key: cord-0968230-7j2rrtwe
authors: Morioka, Ichiro; Toishi, Satoshi; Kusaka, Takashi; Wada, Kazuko; Mizuno, Katsumi
title: Medical care of newborns born to mothers with confirmed or suspected severe acute respiratory syndrome coronavirus 2 infections in Japan
date: 2021-05-27
journal: Pediatr Int
DOI: 10.1111/ped.14855
sha: b5651047fdfc2e9e810b43c4c8a2c0da5f153da9
doc_id: 968230
cord_uid: 7j2rrtwe

BACKGROUND: There are currently no definitive guidelines regarding newborns born to mothers with confirmed severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. This study aimed to investigate the medical care and management that provided or would provide for such newborns. METHODS: The web‐survey was conducted between September and October 2020. A total of 624 hospitals, which generally accept pregnant women for delivery, were involved in this study. The survey included the number of newborns born to mothers with confirmed SARS‐CoV‐2 infection and evaluated the policies regarding the medical care and management of newborns born to mothers with confirmed or suspected SARS‐CoV‐2 infection. RESULTS: Pregnant women with confirmed or suspected SARS‐CoV‐2 infection were accepted or planned to be accepted in 54% (334 hospitals). Out of 52 newborns born to mothers with confirmed SARS‐CoV‐2 infection, one newborn detected a SARS‐CoV‐2 RNA from the nasopharyngeal swab shortly after birth. The types of personal protective equipment during the delivery, the separation of the newborns from the mothers, the SARS‐CoV‐2 testing methods, and the use of incubators during the quarantine period were uniformly provided. However, the methods of ventilatory treatment in the event of respiratory disorders, feeding during maternal isolation, and de‐quarantine and discharge criteria varied. CONCLUSIONS: This survey demonstrated that one newborn detected a SARS‐CoV‐2 RNA shortly after birth out of 52 newborns who were born to mothers with confirmed SARS‐CoV‐2 infection. The policies regarding medical care and management for these newborns in Japan were provided.

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019. The SARS-CoV-2 epidemic began in Japan in March 2020 and the number of patients with SARS-CoV-2 infection increased, mainly involving adults. 1 As the impact of the SARS-CoV-2 on newborns was unknown, during the first and second waves from April to May and from July to August 2020, respectively, many facilities in all regions in Japan-that would accept newborns born to mothers infected with SARS-CoV-2 and would perform neonatal care-were prepared with strict infection control measures based on the tentative information and guidance provided by the Japan Society for Neonatal Health and Development, Centers for Disease Control and Prevention, or the American Academy of Pediatrics. [2] [3] [4] As a result, a certain number of newborns born to mothers with confirmed or suspected SARS-CoV-2 infection was managed in Japan; it indicated that there was an increased burden on neonatal medical care and management in clinical practice. We should consider both the vertical SARS-CoV-2 infection from a mother with COVID-19 to the newborn as well as the horizontal contact or droplet SARS-CoV-2 infection by contact between the mother and the newborn or the newborn and the medical care staff. [2] [3] [4] However, to date, globally, there are no definitive guidelines addressing this situation.

This study aimed to determine the positivity rate of SARS-CoV-2 RNA tests in newborns shortly after birth, born to mothers with confirmed SARS-CoV-2 infection, as of the end of August 2020, to investigate the medical care and management provided or would provide for newborns born to mothers with suspected or confirmed SARS-CoV-2 infection, based on the experience garnered during the first and second waves of the epidemic, and to make comparisons

This article is protected by copyright. All rights reserved among primary delivery handling facilities, regional (secondary) and general (tertiary) perinatal medical centers.

The survey using a dedicated website was conducted by the committee of neonatal medicine in Japan Pediatric Society, 5 from September 1st to October 8th, 2020, when the second wave of the epidemic in Japan was subsiding. By mail, letters were sent to the heads of the pediatric departments at 2507 hospitals in Japan requesting that the online survey be completed, including the uniform resource locator and the quick response code. The respondents answered using the website. This study was approved by the Ethics Committee of the Japan Pediatric Society (number: 2020-12, approved on August 14, 2020). The requirement of formal informed consent was waived because of anonymized data generated from regular practice without any personal information. The objectives of the survey were explained to the respondents on the request letters.

The respondents were asked at the beginning of the survey if they consented to answer.

The survey website was accessed by 1890 pediatricians at hospitals. A total of 1335 responses were obtained. Eight hospitals without the requisite consents and 203 hospitals with duplicated answers were excluded; therefore, 1124 hospitals remained. Of these, 624 (56%) hospitals, where pregnant women are generally accepted for delivery, were finally enrolled and analyzed in this study. The enrolled hospitals were classified based on the three categories specified by the Japan Society of Perinatal and Neonatal Medicine (general perinatal medical centers: 102, regional

This article is protected by copyright. All rights reserved perinatal medical centers: 207, and primary delivery handling facilities: 315). 6

The survey contained questions regarding the current status or policy of medical care and management of newborns born to mothers suspected or confirmed with SARS-CoV-2 infection.

The specific items were: 1) acceptance of pregnant women suspected or confirmed with SARS-CoV-2 infection, 2) number of the newborns with positive SARS-CoV-2 RNA tests shortly after birth, 3) delivery and neonatal resuscitation, and 4) medical care and management of the newborns (locations and negative pressure private rooms, treatments for the newborns with respiratory disorders, SARS-CoV-2 testing, beds during the quarantine period and personal protective equipment (PPE) for medical staff, neonatal feeding while the infected mother was isolated, and de-quarantine and discharge criteria).

For statistical analysis, Pearson's chi-square test was performed for the m×n tables to compare among the groups using Excel statistics (Social Survey Research Information Co., Ltd., Tokyo, Japan). The Clopper-Pearson method was used for 95% confidence intervals. Statistical significance was set at p < 0.05.

Pregnant women suspected or confirmed with SARS-CoV-2 infection were accepted or planned to be accepted in 54% (334/624 hospitals), including 82 general perinatal medical centers (82/102, 80%), 151 regional perinatal medical centers (151/207, 73%), and 101 primary delivery handling

This article is protected by copyright. All rights reserved facilities (101/315, 32%) with a statistically significant difference (p < 0.0001). The general perinatal medical centers exhibited a high acceptance rate of pregnant women suspected or confirmed with SARS-CoV-2 infection (p < 0.0001, Table 1A ).

By August 31, 2020, a total of 52 newborns were born to mothers with confirmed SARS-CoV-2 infection at 31 hospitals (46 [88%] were in 13 special alert prefectures; Tokyo, Osaka, Hokkaido, Ibaraki, Saitama, Chiba, Kanagawa, Ishikawa, Gifu, Aichi, Kyoto, Hyogo, Fukuoka). One newborn detected a SARS-CoV-2 RNA by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) test using a nasopharyngeal swab (1.9%, 95% confidence interval:

The 31 hospitals (9% of the 334 hospitals) managed newborns born to mothers with confirmed SARS-CoV-2 infection, including 13 general perinatal medical centers (13/82, 16%), 9 regional perinatal medical centers (9/151, 6%), and 9 primary delivery handling facilities (9/101, 9%) (p = 0.08).

Of the 324 hospitals that either accepted or planned to accept pregnant women with SARS-CoV-2, the selected delivery modes were vaginal delivery and cesarean section in 33% and 67%, respectively. Vaginal delivery was more common at primary delivery handling facilities than general or regional perinatal medical centers (p = 0.034, Table 1B ). The PPE that was used or planned to be used by the attending neonatologist or pediatrician to receive the newborn, in > 90% of hospitals were gloves, standard gowns, caps, N95 masks, and face shields ( Figure 1 ).

Of the 324 hospitals, resuscitation of newborns was performed or was planned to be performed

This article is protected by copyright. All rights reserved with an infant warmer in the usual delivery room in 60% of hospitals, with an incubator in the same delivery room in 12%, and immediately moved to another room in 28%. Wiping off amniotic fluid at birth in the usual manner was responded by 73%, rinsing with warm saline by 19%, and 8% by other means, of the 322 respondent hospitals.

In most of the 328 hospitals, newborns were either separated or there was a plan to separate the newborn from the infected mother, rather than the newborn remaining in a private room shared with the infected mother wearing PPE (Figure 2A ). Of the 306 hospitals with separation from the infected mother, the main locations for caring for the newborns without respiratory disorders were the neonatal intensive care units, growing care units, and obstetric well-newborn rooms ( Figure   2B ). Forty percent of the hospitals possessed negative pressure private rooms. Negative pressure private rooms were more common in the setting of the general perinatal medical centers than at the other institutions (p < 0.0001, Table 1C ).

If the newborn developed respiratory distress after birth, 65% of the 324 hospitals provided or planned to provide respiratory support with oxygen, such as respiratory ventilation with tracheal intubation and noninvasive positive-pressure ventilation (NPPV). All the general perinatal medical centers (100%) could provide respiratory support with oxygen. When respiratory support was required, 52 and 48% of the hospitals made or planned to make respiratory ventilation by tracheal intubation without NPPV and NPPV before tracheal intubation, respectively (Table 1D) .

This article is protected by copyright. All rights reserved Importantly, 320 (99%) of the 324 hospitals either tested or planned to perform SARS-CoV-2 testing for newborns. SARS-CoV-2 RNA testing was selected by all hospitals (320/320, 100%), such as RT-PCR or loop-mediated isothermal amplification. Eighty-one hospitals (81/320, 25%) also tested or planned to test for SARS-CoV-2 antigen. Materials for the testing were nasopharyngeal swabs in 99%, stool in 13%, and saliva in 3% of the 320 hospitals. The greatest testing frequency was twice, in 61% of the hospitals. Meanwhile, 15% of the hospitals were "not determined" (Figure 3A ). The most common age for the scheduled test was day 0 in 88% of the hospitals ( Figure 3B ).

Thirty-one percent of the 324 hospitals performed or planned to perform usual bathing at the age of one day, 32% within 24 h, and 37% did not perform or plan to perform bathing until the release of the newborns from isolation.

For newborns without respiratory disorders during the quarantine period, 301 (93%) of the 322 hospitals kept or planned to keep the newborns in an incubator, and 21 (7%) placed or planned to place the newborns on cots with > 2 m distances from the other newborns. Figure 4 shows the PPE for medical staff to utilize when performing medical care during the quarantine of newborns. Most hospitals used or planned to use N95 masks or surgical masks, gloves, gowns, caps, and face shields.

Formula milk was used or planned to use for feeding newborns only during the period of isolation of the infected mother; subsequently, expressed breast milk was given, followed by

This article is protected by copyright. All rights reserved breast milk directly from infected mothers wearing PPE ( Figure 5 ), without significant differences between the groups (p = 0.238, Table 1E ).

Two major de-quarantine criteria were as follows: after confirmation of a negative result for the SARS-CoV-2 test and completion of the health observation period (14 days after birth, 40%), and after confirmation of a negative result for the SARS-CoV-2 test (37%). The discharge criteria were the same as usual if a negative result for the SARS-CoV-2 test was confirmed (61%), followed by after the end of the observation period (39%, Figure 6 ).

From September to October 2020, ~80% and 70% of general and regional perinatal medical centers, respectively, had already made preparations for the medical care and management of newborns born to mothers with suspected or confirmed SARS-CoV-2 infection, suggesting that many perinatal centers in Japan accepted or planned to accept such mothers and newborns. The reasons may be that most of the perinatal medical centers in Japan are located at the large hospitals in the regions, where adult patients with COVID-19 are accepted, and they also fulfill the role as perinatal medical centers.

The Centers for Disease Control and Prevention has reported that vertical transmission is rare or uncommon, although concerns about possible intrauterine or intrapartum transmission have been raised. 3 Indeed, the American Academy of Pediatrics and Japanese Society for Neonatal Health and Development have reviewed the literature and reported vertical (intrauterine or intrapartum) infection rates of 1-3% and 0-4.7%, respectively. 2,4 A systematic review using case

This article is protected by copyright. All rights reserved reports and case series from various countries has reported 3-4%. 7, 8 In the present study, the rate was 1.9%, which was similar to these reports.

In the present study, a policy difference was observed in the methods of respiratory support for newborns with respiratory disorders between respiratory ventilation by tracheal intubation without NPPV and NPPV before tracheal intubation. Some neonatologists or pediatricians may consider that because the aerosol infection is a transmission route of SARS-CoV-2, respiratory ventilation by tracheal intubation may pose a lower risk of aerosol infection, although both methods of support induce aerosols. 9 These supportive methods would be provided in a negative pressure private room if possible and the staff should wear full PPE, including N95 masks and eye protection equipment (face shields or goggles). This survey showed that ~70% of general perinatal centers in Japan have negative pressure private rooms.

The main kinds of feeding while the mother was in isolation were the expressed breast milk and formula milk. In only 6% of the hospitals, the newborns were given or planned to be given breast milk directly from infected mothers wearing PPE. The number of hospitals, where the newborns and the infected mother with PPE shared or planned to share a private room, was also extremely limited. Immediately after the start of the SARS-CoV-2 epidemic, the American Academy of Pediatrics recommended that newborns should be separated from infected mothers because the situation was unknown; however, they currently report that the SARS-CoV-2 transmission rate from the infected mother to newborns did not increase if the infected mother observed appropriate infection control measures. 4 The American Academy of Pediatrics and the Japanese Society for Neonatal Health and Development also have stated that there is no need to withhold breast milk because there have been no reported cases of breast milk-acquired SARS-CoV-2 infection, 2, 4 Accepted Article This article is protected by copyright. All rights reserved although there are some reports that SARS-CoV-2 RNA was detected in breast milk. 8, 10, 11 In a systematic review by Walker KF et al., 7 no difference was found in the infection rate in the newborns fed with breast milk and those fed with formula milk, and whether newborns were kept in the same room with the infected mothers or were separated from the infected mothers. At present in Japan, because the infected mothers with SARS-CoV-2 need to be isolated, the newborns cannot be in the same room with the mothers and cannot breastfeed directly.

In some hospitals, the end of the health observation period (14 days after birth) was a criterion for the de-quarantining and discharge of the newborns, in addition to the confirmation of negative SARS-CoV-2 test results. The reason might be that the newborns are considered to be close contacts of the SARS-CoV-2 in utero or during the intrapartum.

As limitations of this study, at the time of this survey, only 31 hospitals experienced the actual delivery of pregnant women with confirmed SARS-CoV-2 infection, therefore, most of the hospitals responded to the assumed policies regarding the medical care and management that would provide for newborns born to mothers with suspected or confirmed SARS-CoV-2 infection.

Nationwide surveys for the actual medical care and management that provided for these newborns should be performed near future (e.g. the actual number of hospitals that gave expressed breast milk). Second, one newborn detected a SARS-CoV-2 RNA by RT-PCR. Because it might be a false-positive result, it is necessary to perform not only SARS-CoV-2 RT-PCR tests using neonatal and maternal materials, such as amniotic fluid, placenta, neonatal nasopharyngeal and anal swabs, and blood, but also serological tests for SARS-CoV-2 IgG and IgM using umbilical cord and neonatal blood from newborns to prove vertical SARS-CoV-2 infection from a mother with COVID-19 to the newborn. 12 Finally, the number of analyzed hospitals was only 1124.

This article is protected by copyright. All rights reserved However, this included 102 general perinatal medical centers and 207 regional perinatal medical centers. Therefore, 94% of the 108 general perinatal medical centers and 69% of the 298 regional perinatal medical centers in Japan were included. It could therefore be assumed that many hospitals, where the medical treatments and care for high-risk newborns are provided, would be covered.

This survey showed for the first time that one newborn detected a SARS-CoV-2 RNA shortly after birth out of 52 newborns who were born to mothers with confirmed SARS-CoV-2 infection.

The types of PPE used during delivery, the separation of newborns from the mothers, SARS-CoV-2 testing methods, and use of incubators during the quarantine period were uniformly provided. However, the methods of ventilatory treatment in the event of respiratory disorders, feeding during the maternal isolation, and the de-quarantine and discharge criteria varied. 

This article is protected by copyright. All rights reserved 

Updates on COVID-19 in Tokyo

Japanese Society for Neonatal Health and Development. Recommended measures on newborn infants born to mothers with suspected or confirmed the new coronavirus infection

Evaluation and management considerations for neonates at risk for COVID-19

FAQs: Management of infants born to mothers with suspected or confirmed COVID-19

Survey on the medical cares and managements for newborns born to pregnant women with confirmed or suspected severe acute respiratory syndrome coronavirus 2 infection (summary)

Japan Society of Perinatal and Neonatal Medicine

Maternal transmission of SARS-COV-2 to the neonate, and possible routes for such transmission: A systematic review and critical analysis. Accepted Article This article is protected by copyright. All rights reserved

Pregnancy and breastfeeding during COVID-19 pandemic: A systematic review of published pregnancy cases

Management of infants born to mothers with suspected or confirmed SARS-CoV-2 infection in the delivery room: A tentative proposal 2020

Detection of SARS-CoV-2 in human breastmilk

Evaluation for SARS-CoV-2 in breast milk from 18 infected women

Vertical transmission of severe acute respiratory syndrome coronavirus 2 from the mother to the infant

Accepted Article

We thank all chief pediatricians of the pediatric departments of the hospitals that participated in this survey. We also thank the following member of the committee of neonatal medicine at the Japan Pediatric Society for their advice and suggestions for this survey; Drs. Hitomi Arahori, 

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All authors have no conflicts of interest to declare in this study.

All authors contributed to the intellectual content of this manuscript. IM wrote the first draft of 

This article is protected by copyright. All rights reserved