Front. Med.

https://doi.org/10.1007/s11684-020-0772-y RESEARCH ARTICLE

Clinical characteristics of 19 neonates born to mothers with

COVID-19

Wei Liu, Jing Wang, Wenbin Li, Zhaoxian Zhou, Siying Liu, Zhihui Rong ( ✉)
Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

© Higher Education Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract The aim of this study was to investigate the clinical characteristics of neonates born to SARS-CoV-2
infected mothers and increase the current knowledge on the perinatal consequences of COVID-19. Nineteen
neonates were admitted to Tongji Hospital from January 31 to February 29, 2020. Their mothers were clinically
diagnosed or laboratory-confirmed with COVID-19. We prospectively collected and analyzed data of mothers and
infants. There are 19 neonates included in the research. Among them, 10 mothers were confirmed COVID-19 by
positive SARS-CoV-2 RT-PCR in throat swab, and 9 mothers were clinically diagnosed with COVID-19. Delivery
occurred in an isolation room and neonates were immediately separated from the mothers and isolated for at least
14 days. No fetal distress was found. Gestational age of the neonates was 38.6  1.5 weeks, and average birth
weight was 3293  425 g. SARS-CoV-2 RT-PCR in throat swab, urine, and feces of all neonates were negative.
SARS-CoV-2 RT-PCR in breast milk and amniotic fluid was negative too. None of the neonates developed clinical,
radiologic, hematologic, or biochemical evidence of COVID-19. No vertical transmission of SARS-CoV-2 and no
perinatal complications in the third trimester were found in our study. The delivery should occur in isolation and
neonates should be separated from the infected mothers and care givers.

Keywords coronavirus disease 2019; severe acute respiratory syndrome-associated coronavirus; maternal-infant infection;
newborn

Introduction Materials and methods

Since December 2019, an atypical pneumonia (coronavirus Patients

disease 2019 (COVID-19)) has been reported to spread
from Wuhan, a beautiful city located at the center of China, All pregnant women who were clinically diagnosed or
to the whole country [1]. The virus is transmitted mainly laboratory-confirmed with COVID-19 during late preg-
via respiratory droplets and/or close contact between nancy, and delivered their babies in Tongji Hospital and
people and family clustering has been reported. Union Hospital West between January 31 and February 29,
It is unclear whether mother-to-infant vertical transmis- 2020 were included in this study. The diagnosis was given
sion is possible, and thus there is no sufficient evidence for following the Coronavirus Pneumonia Prevention and
the prevention and control of neonatal infections. In this Control Chinese Program [2]. Briefly, a clinically diag-
article, we prospectively analyzed the clinical features and nosed COVID-19 case was defined as a case of pneumonia
outcomes of 19 neonates born to mothers suffered from that fulfilled all the following four criteria — fever and/or
severe acute respiratory syndrome coronavirus 2 (SARS- respiratory symptom; radiographic evidence of typical
CoV-2) infection in Tongji Hospital and Union Hospital viral pneumonia (bilateral ground-glass opacities); low or
West, Wuhan from January 31 to February 29, 2020. normal white-cell count or low lymphocyte count; and no
improvement in symptoms after antimicrobial treatment
for 3 days, ruling out common virus infection like
influenza with or without an epidemiologic link to the
Huanan Seafood Wholesale Market or contact with other
Received March 15, 2020; accepted March 17, 2020 patients with similar symptoms. A laboratory-confirmed
Correspondence: Zhihui Rong, [email protected] COVID-19 case was defined as a case with respiratory
2 Features of neonates born to mothers with COVID-19

specimens that tested positive for the SARS-CoV-2 by Most of the mothers’ onset symptom was fever (11/19),
real-time reverse-transcription–polymerase chain reaction 5/19 was cough or dyspnea, 2/19 was diarrhea or other
(RT-PCR) assay for SARS-CoV-2 or a genetic sequence gastrointestinal symptom. Chest CT scan in these pregnant
that matches SARS-CoV-2. women before delivery showed changes of typical of viral
Because there is no neonatal intensive care unit (NICU) pneumonia, such as decreased diffuse and bilateral ground-
in Union Hospital West, all the high risk neonates were glass opacities, patchy lung consolidation, blurred borders,
transferred to NICU, Tongji Hospital. All the inborn and and lesions merged into strips in some cases (Fig. 1). All
outborn neonates were transported to the isolation room in the mothers did not receive prenatal steroid and 6 cases
the NICU to prevent contact with others. The study was received antiviral drugs (200 mg/day oral umifenovir
approved by the Ethic Commission of Tongji Hospital, (Arbidol®, Pharmastandard, Moscow, Russia) for 5 days
Huazhong University of Science and Technology and prior to delivery.
informed consent was obtained from all patients or Delivery occurred in an isolated operating room.
guardians of patients for being included in the study. Eighteen pregnant women delivered their infants by
cesarean section and one by vaginal delivery. No fetal
Data collection distress was found. Three cases had prolonged rupture of
membrane (over 18 h), and thickness of fetal membranes
The maternal information including epidemiological data, was found in one case. The median time between
prenatal data, clinical symptoms, laboratory and radiolo- symptoms and onset of delivery was 4 days (from 1 day
gical characteristics was obtained from electronic medical 8 hours to 10 days). Ten breast milk samples from mothers
records or direct communication with patients and their were obtained after their first lactation and tested for
families. Maternal throat swab samples were collected and SARS-CoV-2 RT-PCR with negative results (Table 1).
tested for SARS-CoV-2 in laboratory of Tongji Hospital,
Huazhong University of Science and Technology by using Clinical characteristics of the neonates
Kit (BioGerm, Shanghai, China), following WHO guide-
lines for RT-PCR. Delivery occurred in an isolation room, after delivery,
The neonates’ information including gender, gestational neonates were immediately separated from their mothers.
age, birth weight, clinical symptoms, laboratory and Twelve newborns were inborn and 7 were outborn. All the
radiological characteristics was obtained from electronic neonates were transferred and isolated in NICU. There
medical records. Neonatal throat swab samples, blood, were 13 male and 6 female infants. Gestational age of the
urine, and feces samples were also collected for testing the neonates was 38.6  1.5 weeks, and average birth weight
presence of SARS-CoV-2. Amniotic fluid samples and was 3293  425 g. No fetal distress was found with the
cord blood were obtained at the time of delivery. APGAR score 8 and 9 at 1 and 5 min, respectively. None of
Additionally, breast milk samples from mothers were the neonates developed clinical, radiologic, hematologic,
collected after their first lactation. Evidence of vertical or biochemical evidence of COVID-19 (Table 2).
transmission was evaluated by testing for the presence of For the laboratory results of the 19 neonates at 24 h of
SARS-CoV-2 in these clinical samples. age: white blood cell counts 16.19  109 (12.1  109 –
18.37  109) cells/L, lymphocyte 3.8  109 (3.03  109
Statistically analysis – 4.75  10 9 ) cells/L, neutrophile 10.84  10 9
(5.99  109 – 13.51  109) cells/L, platelet 295  109
Data are presented by mean  standard deviation (x  s) (224  109 – 312  109) cells/L, C reactive protein 1.2
when the data are normally distributed. Otherwise we used
mg/L (0.2 – 3.7 mg/L), alanine transaminase 10 IU/L (7–18
median (25th percentile–75th percentile) to present.
IU/L), aspartate transaminase 40 IU/L (29–70 IU/L), urea
2.5 mmol/L (1.93–3.7 mmol/L), creatinine 67 μmol/L (60–
Results 78 μmol/L). Seventeen cases took chest X-ray which
showed normal and the rest 2 cases showed increased lung
Clinical characteristics of mothers with COVID-19 marking. SARS-CoV-2 RT-PCR test results in throat swab,
gastric fluid right after birth, urine and feces of all neonates
The median age of mothers was 31 years old (27–34 were negative except one case had positive SARS-CoV-2
years). No mothers had any underlying disease and the RT-PCR in throat swab once. Repeated check on the same
pregnancy was uneventful until the COVID-19 diagnosis. sample showed that the result was false positive.
All the 19 mothers lived in the epidemic area of Hubei Consistently, the virus was undetectable in amniotic fluid
Province. Nine mothers were clinically diagnosed with and umbilical cord blood.
COVID-19 and 10 were laboratory-confirmed with Neonates were immediately separated from the mothers
COVID-19. and isolated for at least 14 days.
Wei Liu et al. 3

Fig. 1 Chest CT scan in 2 pregnant women. Case 10: Decreased diffuse and bilateral ground-glass opacities, patchy lung consolidation, and blurred
borders are shown in the four layers of the chest CT images. Case 11: Patchy lung consolidation and lesions merged into strips are shown in the four
layers of the left lung.

Table 1 Maternal characteristics

Time between Antiviral treat-
Case Throat swab for Age Gestational
Fever Cough Diarrhea symptoms ment before
No. SARS-CoV-2 (year) age (week)
and delivery delivery
1 + 36 36+ 3 Yes No No 21 days No
2 + 26 35+2 Yes Yes No 9 days Yes
3 + 38 38+2 Yes Yes No 7 days Yes
4 + 34 40 Yes No No 8 hours No
5 + 31 41+2 Yes No No 12 days Yes
+4
6 + 34 38 Yes No No 7 days No
7 + 30 39+ 5 No Yes No 10 days Yes
8 + 33 38+2 No No Yes 32 hours No
9 + 34 38+2 Yes No No 4 days No
10 + 33 37+2 No Yes No 21 days Yes
11 – 27 39+ 5 Yes No No 4 days Yes
12 – 30 39+ 1 No No No – No
13 – 26 37+ 5 No No Yes 2 days No
14 – 30 38+ 6 Yes No No 1 day No
+2
15 – 27 41 No No No – No
16 – 26 39 No No No – No
17 – 30 38 Yes No No 1 day No
18 – 33 39 Yes Yes No 2 days No
19 – 33 38 No No No – No

Discussion and, when COVID-19 develops in children, it seems

milder compared to in adult patients. It has been
Children seem less vulnerable to SARS-CoV-2 infection hypothesized that children are less susceptible because
 4

Table 2 Clinical characteristics of neonates

Alanine Aspartate
Case Birth White blood cell Lymphocytes Neutrophil Platelets C-reactive Urea Creatinine
transaminase transaminase
No. weight (g) (109 cells/L) (109 cells/L) (109 cells/L) (109 cells/L) protein (g/L) (mmol/L) (μmol/L)
(IU/L) (IU/L)
1 2840 11.9 2.41 6.91 301 2.2 7 31 3.7 65
2 2500 15.46 4.29 8.23 154 4.2 10 40 2.3 68
3 2920 16.53 3.68 11.41 260 2.2 29 87 2.5 72
4 3250 12.1 7.4 4.2 224 0.1 14 52 1.93 58
5 3470 9.99 2.22 5.99 114 0.2 27 64 1.6 69
6 3250 22.19 3.31 16.4 137 0.1 18 28 1.6 66
7 3670 18 3.8 11.7 208 1.2 24 150 2.1 66
8 3180 10.66 4.01 4.91 342 0.1 6 29 1.64 47
9 3200 13.3 6.34 5.8 289 0.2 10 35 2.5 60
10 3300 16.19 6.34 8.23 312 0.3 15 26 1.5 55
11 3190 8.91 1.9 5.49 299 2.2 8 61 4 84
12 3290 12.44 3.33 7.93 295 1.4 54 340 3.7 56
13 2640 20.66 3.03 14.91 266 0.1 5 25 3.4 82
14 3710 16.88 2.22 13.51 362 9.2 9 54 3.7 62
15 4120 16.14 4.34 10.84 242 2.8 7 35 2.1 87
16 3160 20.9 2.67 16.21 300 10.8 11 70 4.3 78
17 3860 16.48 3.43 11.15 369 0.5 6 26 4.2 67
18 3930 30.43 5.43 21.52 307 1.1 15 89 5.2 95
19 3090 18.37 4.75 11.93 295 3.7 7 38 2.2 82
Median (P25–P75) 16.19 (12.1–18.37) 3.8 (3.03–4.75) 10.84 (5.99–13.51) 295 (224–312) 1.2 (0.2–3.7) 10 (7–18) 40 (29–70) 2.5 (1.93–3.7) 67 (60–78)
MeanSD 3293425 　 　 　 　 　 　 　 　 　
Features of neonates born to mothers with COVID-19
Wei Liu et al. 5

(1) they may be protected by some antibodies against other Management pre- and during delivery
coronaviruses, or (2) they do not develop a strong
inflammatory reaction which is partially responsible for Tongji Hospital and Union Hospital West are both located
the lung injury during COVID-19 [3]. Newborns do not in Wuhan, the epidemic center, so every suspected
have antibodies against other coronaviruses, so theoreti- pregnant women were taken lung CT and SARSCoV-2
cally they maybe more vulnerable to SARS-CoV-2 nucleic acid test prior to delivery. For the clinically
infection. diagnosed or laboratory-confirmed cases, an expert team of
In our research, none of the samples from different body physicians including epidemiologist, virologists, infec-
part of the neonates, maternal amniotic fluid, and breast tious disease specialists, obstetricians, neonatologists was
milk were detected for SARS-CoV-2 positive. None of the informed soon after the admission. All the specialists
19 neonates developed clinical, radiologic, hematologic, or decided the prenatal treatment and the best time for
biochemical evidence of COVID-19. This results are delivery and delivery mode. In this current research, the
partially consistent with Chen et al.’s study, which showed smallest gestational age was 35 weeks and no mothers
9 SARS-CoV-2 infected pregnant women do not seem to received prenatal steroid and 6 mothers received antiviral
develop a more severe COVID-19 compared to non- drugs (200 mg/day oral umifenovir (Arbidol®, Pharmas-
pregnant patients, and the consequence of their neonates tandard, Moscow, Russia)) for 5 days prior to delivery. No
were relatively well [4]. complication of prenatal antivirus treatment on the new-
borns were found in this study.
Zero neonate infection rate Delivery occurred in an isolated operating room. All the
surgeons, nurses, and other staffs in the operating room
The zero neonate infection rate in our study may be due to were wearing level 3 protective clothing. Most of the
the following reasons. pregnant women delivered their infants by cesarean section
and only one by vaginal delivery. A neonatal transport
Lack of evidence to support vertical transmission team specializing in infection control performed the
of SARS-CoV-2 from mothers suffered from transfer to a previously designated tertiary neonatal unit
COVID-19 during the last trimester of pregnancy (Tongji Hospital). The mother and newborn need to be
isolated separately until both are cleared, pending further
In a broad spectrum, mother to infant transmission includes clinical outcome data.
intrauterine vertical transmission, maternal blood and
amniotic fluid contact during delivery, and postnatal Postnatal observation and management
infection, especially during breastfeeding. In a narrow
spectrum, mother to infant transmission only refers to Zeng et al. [13] and Wang et al. [14] reported two cases of
intrauterine vertical transmission. To confirm whether there newborn suffered from SARS-CoV-2 infection, one case
is intrauterine vertical transmission or not, this study carried was 17 days, the other one was 19 days after birth, and all
out SARSCoV-2 nucleic acid detection of breast milk, cord of them were infected through family contact transmission,
blood, amniotic fluid, neonatal throat swab, feces and urine suggesting that more attention should be paid to newborn
sample of the newborns. The results showed that all the test caregiver, to prevent close contact transmission. Therefore,
samples were negative, so the results of this study did not in this study, after the initial resuscitation, the newborn was
support the intrauterine vertical transmission. Our results immediately isolated from the mother and family mem-
are consistent with another series publication, where no bers, transferred to the neonatal isolation ward (class III A)
neonates were found positive to SARSCoV-2 [5]. Several for further observation. Contact with the non-infected
case reports of neonates born to COVID-19 mother are also parent and family members was minimized and level II
consistent with our results [6–9]. protective clothing for all medical staffs was required.
Recent data indicated that angiotensin-converting Medical wastes were isolated in double-layer medical
enzyme-2 receptors have very low expression in the waste bags and disinfected before disposal. Non-disposa-
placenta, which makes the chance of SARS-CoV-2 vertical ble fabrics were collected into double layer medical waste
transmission likely impossible [10]. Chen et al.’s research bags and transported to the hospital disinfection center as
indicated that the placenta of infected mother lacked the per hospital protocol.
morphological changes related to virus infection, and Supportive care was provided by specialized infection
SARSCoV-2 nucleic acid in placenta was undetectable prevention medical team. Invasive procedures such as
[11]. However, it remains unclear if the maternal viral venepuncture and blood sampling were minimized as
charge or timing of SARS-CoV-2 infection may influence much as possible. Monitoring included vital signs, oxygen
the transmission [12]. saturation, blood glucose, intestinal motility and neonatal
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