The consequences of severe acute respiratory syndrome corona virus 2 on mother and fetus remain unknown due to a lack of robust evidence from prospective studies.
This study evaluated the effect of coronavirus disease 2019 (COVID-19) on neonatal outcomes and the scope of vertical transmission.
This ambispective observational study enrolled pregnant women with COVID-19 in North India from April 1 to August 31, 2020 to evaluate neonatal outcomes and the risk of vertical transmission.
A total of 44 neonates born to 41 COVID-19–positive mothers were evaluated. Among them, 28 patients (68.3%) (2 sets of twins) were delivered within 7 days of testing positive for COVID-19, 23 patients (56%) (2 sets of twins) were delivered by cesarean section; 13 newborns (29.5%) had low birth weight; 7 (15.9%) were preterm; and 6 (13.6%) required neonatal intensive care unit admission, reflecting an increased incidence of cesarean delivery and low birth weight but zero neonatal mortality. Samples of cord blood, placental membrane, vaginal fluid, amniotic fluid, peritoneal fluid (in case of cesarean section), and breast milk for COVID-19 reverse transcription-polymerase chain reaction tested negative in 22 prospective delivery cases. Nasopharyngeal swabs of 2 newborns tested positive for COVID-19: one at 24 hours and the other on day 4 of life. In the former case, biological samples were not collected as the mother was asymptomatic and her COVID-19 report was available postdelivery; hence, the source of infection remained inconclusive. In the latter case, all samples tested negative, ruling out the possibility of vertical transmission. All neonates remained asymptomatic on follow-up.
COVID-19 does not have direct adverse effects on the fetus per se. The possibility of vertical transmission is almost negligible, although results from larger trials are required to confirm our findings.
With evolving coronavirus disease 2019 (COVID-19) pandemic and the new data emerging, though minimal, the possibility of vertical transmission cannot be denied. Further, the impact of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) on perinatal outcome is also uncertain. Most studies are retrospective and included third trimester patients. However, long-term prospective studies evaluating the effect on second and third trimester are lacking. Few studies reported increased incidence of cesarean, preterm labor, low birth weight, and NICU admission [
Objectives of this study were to evaluate the scope of vertical transmission, if any, and to evaluate the effect of COVID-19 on neonatal outcome.
In this ambispective (including retrospective and prospective cases) observational study, approved by the institutional ethics committee (GIMS/IEC/HR/2020/13), we included real-time reverse transcription-polymerase chain reaction (RT-PCR) confirmed COVID-19 pregnant patients admitted at our institute from 1st April 2020 to 31st August 2020 after obtaining their written informed consent. Universal screening of pregnant patients admitted at our institute (whether symptomatic or asymptomatic) was being practiced as per regional guidelines. The inclusion criteria were symptomatic/asymptomatic RT-PCR confirmed COVID-19 pregnant patients in second and third trimester. The exclusion criteria were patients without RT-PCR confirmed COVID-19 disease, patients in first trimester, and postpartum patients.
The recruited patients were managed as per the national COVID-19 guidelines for the pregnant patients [
The recruited patients who were discharged antenatally were followed for delivery till the period of study. The records of those who delivered outside at non- COVID facility were retrieved for delivery details, neonatal outcome, and any neonatal complication during follow-up period (
For statistical analysis, continuous variables were described as mean (standard deviation) or median (interquartile range). Categorical variables were represented as frequencies with proportions. We used software EpiInfo 7.2 (CDC, Atlanta, GA, USA) for analysis of data.
We reported the outcome of 44 neonates born to 41 COVID-19 infected females (including 3 twin gestations) from 1st April 2020 to 31st August 2020 at our institute. Out of 102 pregnant COVID patients we included 57 eligible pregnant patients, 12 second trimester, and 45 third trimester with RT-PCR confirmed COVID-19 infection in the study with 6 cases being retrospective (
Out of 41 females with COVID-19 infection, over two-thirds (28 [68.3%]) delivered within 7 days from being tested positive (viral detection- delivery interval); 23 (56%) underwent cesarean section with fetal distress and previous cesarean section being most common indications. Among the patients who delivered at our institute 22 (78.6%) delivered at term while 6 (21.4%) delivered before 37 completed weeks. All deliveries outside our institute at non-COVID facility were term (
Among 28 patients delivered at our institute, for 22 prospective study participants, we sent the biological samples – cord blood, placental membrane swab, vaginal fluid swab, amniotic fluid, peritoneal fluid (in 10 cases of cesarean section), and breast milk for COVID-19 RT-PCR to evaluate the scope of vertical or horizontal transmission and all tested negative (
Out of 44 newborns, low birth weight was reported among 13 neonates (29.5%); 7 neonates (15.9%) were preterm; 24 (54.5 %) were males; 5 (11.4%) had Apgar score <7 at 5 minutes and 6 (13.6%) required neonatal intensive care unit (NICU) admission mainly for prematurity and birth asphyxia. There was no stillbirth or neonatal death. Majority had near normal biochemical profile and no severe neonatal complications.
A total of 23 (52.2%) were roomed in and breast fed. All neonates were followed till 2 weeks without any reported untoward outcome. The detailed outcome of neonates delivered at our institute and those delivered after being discharged at non-COVID facility have been tabulated in
To our knowledge, this is the first ambispective study from North India with a significant cohort of prospective study participants describing the outcome of neonates born to the COVID-19 positive mothers and the risk of perinatal transmission of COVID-19. Most of the studies are retrospective barring few [
We report 14.6% preterm delivery rate in our study. Earlier studies have reported very high incidence ranging from 36.4% to 60% [
Mean viral detection-delivery interval in our study was 7.97±8.45 days which was much higher than that reported by Smith et al. [
Yan et al. [
Neonates can get infected via vertical transmission or through contact. The vertical transmission broadly includes transmission of infection in-utero, during delivery or during breastfeeding and to detect its possibility various biological samples need to be tested. Centers for Disease Control and Prevention reported 2.6% incidence of neonatal COVID-19 [
We proceeded with the study as sporadic case reports and case series tested one or the other biological sample positive warranting further research to assess the risk of vertical transmission. Penfield et al. [
Various studies reported 9%–22.2% incidence of low birth weight [
In our study 29.2% had low birth weight, 88.6% had Apgar score more than 7 at 5 minutes, 11.4% neonates had birth asphyxia, 13.6% NICU admission with no neonatal death. This is in accordance with the prospective study conducted by Salvatore et al. [
In the initial phase of pandemic, various guidelines advocated immediate separation of neonates from mothers after delivery considering COVID-19 highly infectious. Once it became clear with the emerging evidence that the breast milk does not contain viable virus and the risk of neonatal COVID-19 infection is similar in those separated from mothers and those being roomed in with infection prevention and control practices in place, the guidelines were revised. Although World Health Organization [
We followed up the neonates after birth till 2 weeks or discharge whichever was later. Follow-up of neonates is essential to detect late infection or any other complication. In most of the studies, this neonatal follow-up was lacking. In the prospective study by Salvatore et al. [
The strengths of our study include prospective cohort with good sample size; testing of all the biological samples for vertical transmission and follow-up of neonates for the COVID-19 symptoms. There are certain limitations too; comparison with non-COVID-19 pregnant patients would have enlightened the difference in neonatal outcome, if any, which was not possible in our setting as ours was a dedicated tertiary COVID-19 center. Also, antibody testing may have added to the evidence related to vertical transmission though the possibility is trivial Further, the findings in our study may not be generalized as it is a single center study.
Our study concludes that COVID-19 is not associated with increased adverse neonatal outcome; even most of the infected neonates remain asymptomatic. Further, as per evidence generated, the possibility of vertical transmission of COVID-19 is extremely low. Larger prospective studies with neonatal follow-up are needed to provide robust evidence related to the scope of perinatal transmission if any.
No potential conflict of interest relevant to this article was reported.
We would like to thank all the residents, nursing staff, and the laboratory staff involved in the management of these motherneonate dyads.
Flow chart of study design. COVID-19, coronavirus disease 2019; RT-PCR, reverse transcription-polymerase chain reaction.
Outcomes of recruited pregnant COVID-19–positive patients. COVID-19, coronavirus disease 2019; LSCS, lower segment cesarean section; LBW, low birth weight; NICU, neonatal intensive care unit.
Outcome of neonates borne to COVID-19–positive mothers (n=44)
Parameter | Delivered at our institute |
Delivered at non-COVID facility after discharge |
Overall |
|
---|---|---|---|---|
Delivery details | (n=28) | (n=13) | (n=41) | |
Mode of delivery | ||||
Vaginal delivery | 13 (46.4) |
5 (38.4) | 18 (44) |
|
Cesarean delivery | 15 (53.5) |
8 (61.5) |
23 (56) |
|
Indication of cesarean delivery | ||||
Fetal distress | 6 (21.4) | 2 (15.3) | 8 (19.6) | |
Previous cesarean delivery | 5 (17.8) | 3 (23) | 8 (19.6) | |
Breech presentation | 1 (3.5) | 2 (15.3) | 3 (7.3) | |
Cephalopelvic disproportion | 1 (3.5) | 0 (0) | 1 (2.4) | |
Nonprogress of labor | 0 (0) | 1 (7.6) | 1 (2.4) | |
Term PROM with failed induction | 2 (7.1) | 0 (0) | 2 (4.8) | |
Viral detection-delivery interval (day) | 2.89±1.62 | 18.92±6.46 | 7.97±8.45 | |
<7 | 28 (100) | 0 (0) | 28 (68.3) | |
8–14 | 0 (0) | 4 (30.7) | 4 (9.7) | |
>14 | 0 (0) | 9 (69.2) | 9 (21.95) | |
Single or multiple gestations | ||||
Singleton | 26 (92.8) | 12 (92.3) | 38 (92.6) | |
Twin | 2 (7.1) | 1 (7.6) | 3 (7.3) | |
Gestational age at the time of delivery (wk) | ||||
28–32 | 1 (3.6) | 0 (0) | 1 (2.4) | |
32–34 | 2 |
0 (0) | 2 (4.9) | |
34–36.6 | 3 (10.7) | 0 (0) | 3 (7.3) | |
>37 | 22 |
13 |
35 (85.4) | |
Vertical transmission | ||||
Positive neonatal Nasopharyngeal RT-PCR for COVID-19 (n=30) | 2 (6.6) | Not done | ||
Biological Samples for COVID-19 RT-PCR (n=22) | Not done | |||
Cord blood | Negative in all (100) | |||
Placental membrane swab | Negative in all (100) | |||
Vaginal fluid | Negative in all (100) | |||
Amniotic fluid | Negative in all (100) | |||
Peritoneal fluid (n=10 CS) | Negative in all (100) | |||
Breast milk for COVID-19 RT-PCR (n=23) | Negative in 23 (100) | Not done | ||
Neonatal details | (n=30) | (n=14) | (n=44) | |
Maturity | ||||
Term | 23 (76.6) | 14 (100) | 37 (84.1) | |
Preterm | 7 (23.3) | 0 (0) | 7 (15.9) | |
Birth weight (kg) | 2.51±0.64 | 2.79±0.33 | 2.60±0.57 | |
>2.5 | 19 (63.3) | 12 (85.7) | 31 (70.4) | |
1.5–2.5 | 9 (30) | 2(14.2) | 11 (25) | |
<1.5 | 2 (6.6) | 0 (0) | 2 (4.5) | |
Sex | ||||
Male | 16 (53.3) | 8 (57.1) | 24 (54.5) | |
Female | 14 (46.6) | 6 (42.8) | 20 (45.5) | |
Apgar score | ||||
<7 at 5 min | 5 (16.6) | 0 (0) | 5 (11.4) | |
>7 at 5 min | 25 (83.3) | 14 (100) | 39 (88.6) | |
Birth asphyxia | 5 (16.6) | 0 (0) | 5 (11.4) | |
NICU admission | 6 (20) | 0 (0) | 6 (13.6) | |
Neonatal death | 0 (0) | 0 (0) | 0 (0) | |
Roomed in & breast fed | 9 (30) | 14 (100) | 23 (52.2) |
Values are presented as number (%) or mean±standard deviation.
COVID-19, coronavirus disease 2019; PROM, premature rupture of membranes; RT-PCR, reverse transcription-polymerase chain reaction; CS, cesarean section; NICU, neonatal intensive care unit.
One twin delivery.
Two twin deliveries.
Three twin deliveries.
Details of 2 COVID-19–positive neonates
Parameter | Case 1 | Case 2 | ||
---|---|---|---|---|
Neonatal details | ||||
Maturity | Term | Term | ||
Mode of delivery | Vaginal delivery | Cesarean delivery (abruption) | ||
Infection-delivery interval (day) | 1 | 4 | ||
Birth weight (kg) | 2.6 | 2.25 | ||
Sex | Female | Male | ||
Apgar score at 5 min | 8 | 8 | ||
Positive nasopharyngeal RT-PCR | 24 hours | 4th day | ||
Negative nasopharyngeal RT-PCR | 4th ,7th postnatal day | 7th, 10th postnatal day | ||
Biological samples | Not collected | Collected | ||
Vaginal fluid | Not done | Negative | ||
Amniotic fluid | Not done | Negative | ||
Placental membrane swab | Not done | Negative | ||
Cord blood | Not done | Negative | ||
Breast milk for RT-PCR | Negative | Negative | ||
Roomed in, breast fed | Yes | No | ||
Contact with mother | Yes | No, separated immediately from mother and kept in NICU | ||
Symptoms in neonate | Asymptomatic | Asymptomatic | ||
Investigations of neonate day 1 | ||||
Hemoglobin (gm/dL) | 16.4 | 18.9 | ||
Total leucocyte count (cells/mm3) | 17,600 | 18,500 | ||
Differential leucocyte count (%) | P67, L26, E3, M4 | P71, L20, E6, M3 | ||
Platelet count (lac/mm3) | 1.84 | 1.93 | ||
Bilirubin (mg/dL) | 0.8 | 1.1 | ||
Alanine aminotransferase (IU/L) | 19 | 24 | ||
Aspartate aminotransferase (IU/L) | 48 | 62 | ||
Urea (mg/dL) | 16.4 | 15.2 | ||
Creatinine (mg/dL) | 0.89 | 1.0 | ||
Hospital stay (day) | 7 | 10 | ||
Maternal characteristics | ||||
COVID status at admission | Suspect (from hotspot/cluster area) | Positive | ||
Age (yr) | 29 | 26 | ||
Parity | G5P4L4 (previous normal delivery) | G2P1L1 (previous cesarean) | ||
Symptoms in mother | Asymptomatic | Asymptomatic | ||
GA on admission | 38 weeks 5 days | 37 weeks 5 days | ||
Pregnancy associated complications | No | Antepartum hemorrhage (abruption) | ||
Comorbidity | No | No |
COVID-19, coronavirus disease 2019; RT-PCR, reverse transcription-polymerase chain reaction; NICU, neonatal intensive care unit; GA, gestational age.