key: cord-0942211-7v2f4g2f authors: Romano-Keeler, J.; Fiszbein, D.; Zhang, J.; Horowitz, J.; Hayani, K.; Buhimschi, I.; Lopez, C.; Kadhem, Z.; Berman, J.; Rasamimari, P.; Raghavan, A.; Pillers, D.-A. M.; Sun, J. title: Center-Based Experiences Implementing Strategies to Reduce Risk of Horizontal Transmission of SARS-Cov-2: Potential for Compromise of Neonatal Microbiome Assemblage date: 2021-01-08 journal: medRxiv : the preprint server for health sciences DOI: 10.1101/2021.01.07.21249418 sha: 26829e07a97482a9faf44c738aba4190125efebd doc_id: 942211 cord_uid: 7v2f4g2f Perinatal transmission of COVID-19 is poorly understood and many neonatal intensive care units' (NICU) policies minimize mother-infant contact to prevent transmission. We present our unit's approach and ways it may impact neonatal microbiome acquisition. We attending COVID-19 positive mothers' deliveries from March-August 2020. Delayed cord clamping and skin-to-skin were avoided and infants were admitted to the NICU. No parents' visits were allowed and discharge was arranged with COVID-19 negative family members. Maternal breast milk was restricted in the NICU. All twenty-one infants tested negative at 24 and 48 hours and had average hospital stays of nine days. 40% of mothers expressed breastmilk and 30% of infants were discharged with COVID-19 negative caregivers. Extended hospital stays, no skin-to-skin contact, limited maternal milk use, and discharge to caregivers outside primary residences, potentially affect the neonatal microbiome. Future studies are warranted to explore how ours and other centers'with similar policies influence this outcome. Since its presentation in Wuhan, China, coronavirus disease of 2019 caused by 55 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into a global 56 pandemic with significant mortality and morbidity. The number of confirmed cases has climbed 57 to over thirty million with one million deaths in more than 200 countries and territories. (1, 2) 58 While initially associated with fever, cough and shortness of breath, presentation of this virus 59 has progressed to include gastrointestinal (GI) symptoms either in isolation or in conjunction (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 8, 2021. ; https://doi.org/10.1101/2021.01.07.21249418 doi: medRxiv preprint nascent microbiome or how policies to prevent perinatal COVID transmission may affect 80 newborn microbial colonization (Figure 1 ). Twenty-one patients born to COVID-19 positive mothers were admitted to the NICU per 82 University of Illinois at Chicago (UIC) guidelines. In this paper, we review NICU courses, 83 including the incidence viral transmission. We explore ways that our guidelines, designed to 84 reduce risk of viral transmission to infants, may impact composition of the newborn microbiome. Finally, we discuss future directions for NICU management that minimize perinatal viral 86 transmission, promote normal early life microbiome assemblage, and optimize short and long-87 term health outcomes. This study was approved by the UIC Institutional Review Board (protocol no. 2020-0443). Neonatal teams attended deliveries of all COVID-19 positive mothers from March-August 2020. Deidentified maternal data collected included age, reported race, dates and types of COVID-19 93 testing, COVID-related symptoms at delivery, and details on peripartum courses including 94 intrapartum antibiotics and timing of rupture of membranes (Table 1) . Delayed cord clamping and skin-to-skin contact were avoided, including physical contact with 96 family members and infants were admitted to the NICU with contact isolation. Metadata 97 obtained on infants included delivery indication and mode, Apgar scores, gestational age, birth 98 weight, and gender. Respiratory and/or gastrointestinal symptoms were recorded throughout 99 hospitalization and POCT was completed at 24 and 48 hours of life. Visitors were not allowed 100 during NICU stays. Discharges were arranged whenever possible with COVID-19 negative 101 caregivers. No expressed breastmilk was used in the NICU but mothers were encouraged to 102 pump and store milk and instructed on how to safely breastfeed at home. Information on feeding 103 regimen after discharge was recorded when available from outpatient clinic notes. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 8, 2021. ; https://doi.org/10.1101/2021.01.07.21249418 doi: medRxiv preprint Twenty-one COVID-19 positive mothers positive delivered during this study with a mean (range) 108 age of 26 (17-42) years. Approximately 62% of mothers were African American (n=13) and 5% were Latinx (n=5). COVID-19 antigen detection via rapid point of care testing (POCT) within 72 110 hours of delivery or as an inpatient in labor and delivery was positive in 90% of mothers (n=19). The remaining two mothers had positive viral PCR tests collected prior to delivery. 123 grams, respectively. Prematurity complicated two deliveries, including one case where an infant 124 was delivered early due to the severity of mother's COVID-19 infection. In 40% of cases (n=8), 125 delayed cord clamping occurred and in 10% (n=2) of deliveries, mothers were allowed skin-to-126 skin contact. Approximately 70% of infants were male with a mean one minute Apgar score of 7 127 and a 5 minute score of 9. POCT was negative at 24 and 48 hours for all infants. In addition, 128 two infants had a third POCT due to persistent oxygen requirements, which were also negative. More than half of patients (n=11) required respiratory support including mechanical ventilation 130 All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 8, 2021. Maternal complications from COVID-19 may contribute to C-sections. However, in our study, 155 this was the case in only one patient. Other studies of COVID-19 and pregnancy outcomes 156 All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 8, 2021. ; report an increases in C-sections due to fetal distress even in asymptomatic mothers, which 157 may impact the neonatal microbiome. (17, 19) 158 Vaginal deliveries represent one of the earliest exposures of newborns to microbes. (20, 21) 159 These pioneer bacteria initiate intestinal eubiosis and impart optimal health outcomes, including 182 All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 8, 2021. ; https://doi.org/10. 1101 /2021 In conclusion, while adopting approaches to minimize viral transmission, we and other (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 8, 2021. ; https://doi.org/10.1101 https://doi.org/10. /2021 (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Table 1 . Clinical Characteristics of COVID positive mother-infant dyads 16 17 18 All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 8, 2021. ; https://doi.org/10.1101/2021.01.07.21249418 doi: medRxiv preprint Revised Estimates for the Number of Human and Bacteria 214 Cells in the Body Manifestations and prognosis of 216 gastrointestinal and liver involvement in patients with COVID-19: a systematic review and meta-217 analysis Gastrointestinal symptoms, pathophysiology, and treatment in 219 COVID-19 Epidemiological, clinical and 222 virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with 223 gastrointestinal symptoms FAQs: Management of Infants Born to Mothers with Suspected or 227 Confirmed COVID-19 COVID-19 in a 26-week preterm neonate The microbiome in early life: implications 233 for health outcomes Early infancy microbial and metabolic alterations affect risk of childhood asthma Early life establishment of site-specific microbial communities in the gut Maternal influences on fetal microbial colonization and 241 immune development Gastroenterology Clinics of North America Dynamics 245 and Stabilization of the Human Gut Microbiome during the First Year of Life Maternal 248 inheritance of bifidobacterial communities and bifidophages in infants through vertical 249 transmission Maternal and perinatal outcomes with COVID-19: A 251 systematic review of 108 pregnancies Births: Final Data for 2018. Natl 253 Vital Stat Rep Outcome of 255 coronavirus spectrum infections (SARS, MERS, COVID-19) during pregnancy: a systematic 256 review and meta-analysis 258 Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body 259 habitats in newborns Maturation of the 261 infant microbiome community structure and function across multiple body sites and in relation to 262 mode of delivery Childhood overweight after 264 establishment of the gut microbiota: the role of delivery mode, pre-pregnancy weight and early 265 administration of antibiotics Prenatal and post-267 natal exposure to antibiotics and risk of asthma in childhood Pediatrics AAo. Breastfeeding Guidance Post Hospital Discharge for Mothers or Infants 275 with Suspected or Confirmed SARS-Co V-2 Infection CoV-2 and human milk: what is the evidence? medRxiv. 2020 Pediatrics AAo. FAQs: Management of Infants Born to Mothers with Suspected or 281 Confirmed COVID-19 Gut-lung axis and dysbiosis in COVID-19 Targeting the gut-lung microbiota axis by means of a high-fibre 285 diet and probiotics may have anti-inflammatory effects in COVID-19 infection