Viewpoint Arch Dis Child Fetal Neonatal Ed: first published as 10.1136/archdischild-2020-319372 on 14 June 2020. Downloaded from

affected earlier in the pandemic. Data National active surveillance to describing the neonatal impact of maternal management of COVID-19 understand and inform neonatal care are vital to inform maternity care and neonatal service delivery. Moreover, in COVID-19 information describing both the severity of COVID-19 and current management Chris Gale ‍ ,1 Marian Knight ‍ ,2 Shamez Ladhani,3,4 is key to informing treatment, ideally 5 6 7 8 in the context of randomised trials. Elizabeth S Draper ‍ , Don Sharkey, Cora Doherty, Helen Mactier, Large, national, adaptive trials have Jennifer J Kurinczuk,2 On behalf of Members of Neonatal Complications been rapidly developed, including the Randomised Evaluations of COVID-19 of COVID-19 Surveillance Group Therapy Trial (​www.​recoverytrial.​net), comparing multiple potential treat- The novel coronavirus severe acute respi- transmission of SARS-­CoV-2 has yet ments for COVID-19. Although this ratory syndrome coronavirus 2 to be definitively established; neonatal trial predominantly targets adults, preg- (SARS-­CoV-2) causes COVID-19 and has infection with the virus has been nant women and children (including spread rapidly. COVID-19 was declared a detected in the first days after birth to neonates) are eligible, and enrolment pandemic by the WHO on 12 March mothers with COVID-191; however, should be considered in severe disease. 2020. Robust, population-based­ data this could represent early horizontal Given the critical relevance of inci- describing COVID-19 during pregnancy transmission. Support for vertical trans- dence data, it is important to note that and the neonatal period are critical to mission comes from serological testing much currently available information understand and manage this global threat following maternal COVID-19, which comes from limited case series or single-­ in these groups. found SARS-­CoV-2 IgM in umbilical centre studies rather than population-­ There are three key ways that cord blood2; however, SARS-CoV­ -2 viral based surveillance, which is more robust, SARS-­CoV-2 could affect neonates: RNA was not detected in these newborns, objective and less likely to be biased 1. Vertical transmission of SARS-­CoV-2 and the validity of current serological by local practices and protocols. Accu- from mother to infant, which may lead tests remains to be established.3 Never- rate population-level­ incidence data are to neonatal COVID-19. theless, neonates can be symptomatic essential, and acquisition of such data 2. Horizontal transmission of SARS-­ with COVID-19 regardless of the mech- requires active population surveillance; copyright. CoV-2 in the neonatal period, poten- anism of transmission. Although initial this differs from generally unrepresen- tially leading to neonatal COVID-19; data indicated that the disease was less tative data collected through registries this may occur from family contacts or severe in children,4 approximately 10% that are unable to inform incidence or nosocomial transmission in healthcare of neonates and infants with COVID-19 complication rates at population level. settings, such as neonatal units. develop severe or critical disease, a The British Paediatric Surveillance Unit 3. Indirect effects on the newborn fol- higher proportion than that in any other (BPSU) has pioneered active surveil- lowing maternal COVID-19 that im- paediatric age group.5 The wider impact lance for rare diseases in the UK and pact pregnancy or labour and birth, of maternal COVID-19 on the offspring internationally since 1985. The orange leading to complications, such as is even less well understood. Several card system developed by the BPSU has preterm birth. This will include situa- hundred cases of COVID-19 and asymp- been an exemplar for the development tions where the neonate is affected by, tomatic SARS-­CoV-2 infection6 have of national surveillance in other special- but does not contract, SARS-­CoV-2. been reported in pregnancy, and while ties (such as UK Obstetric Surveillance The impact of COVID-19 on the majority of newborns were asymp- System (UKOSS)) and internationally. neonates, as well as the importance of tomatic, cases of preterm birth and one Crucially, BPSU contacts paediatricians http://fn.bmj.com/ these different potential mechanisms neonatal death (a preterm infant negative and neonatologists across the UK and of exposure, remains unclear. Vertical for SARS-­CoV-2) have been reported.7 Ireland every month and asks them to Higher rates of stillbirth and preterm report whether they have managed a delivery were found in women affected case of any condition under active BPSU 1 Neonatal Medicine, School of Public Health, Faculty of by the 2009/H1N1 influenza pandemic.8 surveillance. A response is requested Medicine, Imperial College London, London, UK A similar pattern, if seen in SARS-CoV­ -2, even if no cases were encountered; this on October 2, 2021 by guest. Protected 2NIHR Policy Research Unit in Maternal and Neonatal Health and Care, National Perinatal Epidemiology Unit, may result in higher requirements for ensures high case ascertainment with University of Oxford, Oxford, UK neonatal cots and additional morbidity more than 90% of paediatrician and 3Immunisation Department, Public Health England, and mortality. neonatologists responding to the BPSU London, UK 4 Measuring the incidence of neonatal every month. This methodology enables Paediatric Infectious Diseases Research Group, St. accurate estimation of regional and George’s University of London, London, UK complications of COVID-19 accurately 5Health Sciences, University of Leicester, Leicester, UK and comprehensively is therefore crit- national incidence, clinical and outcome 6Academic Child Health, School of Medicine, University ical to provide optimal advice and care. data in rare diseases in children. of Nottingham, Nottingham, UK A BPSU study on neonatal complica- 7 Understanding rates of vertical and peri- Neonatology, University Hospital Wales, Cardiff, UK natal horizontal transmission is essen- tions of COVID-19 has been developed 8Neonatology, Princess Royal Maternity, Glasgow, UK tial to inform newborn care following to perform active surveillance to address Correspondence to Dr Chris Gale, Neonatal birth to an affected mother, where key uncertainties related to COVID-19 Medicine, School of Public Health, Faculty of Medicine, in neonates. Any neonate that meets the Chelsea and Westminster campus, Imperial College current UK practice—keeping mother London, London SW10 9NH, UK; and newborn together and encouraging surveillance case definition (box 1) in the christopher.​ ​gale@imperial.​ ​ac.uk​ breastfeeding—differs from countries UK should be reported to the BPSU. For

F346 Arch Dis Child Fetal Neonatal Ed July 2020 Vol 105 No 4 Viewpoint Arch Dis Child Fetal Neonatal Ed: first published as 10.1136/archdischild-2020-319372 on 14 June 2020. Downloaded from

Box 1 British Paediatric Surveillance Unit surveillance case definition for neonatal complications of COVID-19

Any baby or infant 1. That has a diagnosis of COVID-19 made on a sample taken before 29 days of age Open access This is an open access article distributed and receives inpatient care for COVID-19 (this includes postnatal ward, neonatal unit, in accordance with the Creative Commons Attribution paediatric inpatient wards and paediatric intensive care units) or Non Commercial (CC BY-­NC 4.0) license, which permits 2. Where the mother had confirmed COVID-19 at the time of birth or suspected others to distribute, remix, adapt, build upon this work COVID-19 at the time of birth that has subsequently been confirmed, and the baby non-­commercially, and license their derivative works on was admitted for neonatal care. different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-­commercial. See: http://​ creativecommons.org/​ ​licenses/by-​ ​nc/4.​ ​0/. the first time, the BPSU is asking for cases has been established at St Georges Hospital © Author(s) (or their employer(s)) 2020. Re-­use of neonatal complications of COVID-19 in collaboration with PHE. This seeks to permitted under CC BY-­NC. No commercial re-­use. See to be reported weekly to capture more recruit pregnant women with COVID-19 rights and permissions. Published by BMJ. timely data to inform clinical care; this to collect antenatal, perinatal and post- ►► Additional material is published online only. To will be reviewed as the pandemic evolves natal samples for viral and serological view, please visit the journal online (http://dx.​ doi​ .org/​ ​ (data collection form: online supple- testing. Further initiatives are seeking to 10.1136/​ ​archdischild-2020-​ ​319372). mentary file 1). For more complete case understand the impact of COVID-19 on ascertainment, this BPSU surveillance neonatal services (https://​public.​vtoxford.​ will link with other related data sources, org/​covid-​19/). including ongoing UKOSS surveillance Available data suggest that most of COVID-19 in pregnancy for maternal infants and children with COVID-19 To cite Gale C, Knight M, Ladhani S, et al. Arch Dis Child Fetal Neonatal Ed 2020;105:F346–F347. cases, Mothers and Babies: Reducing Risk develop mild to moderate illness only. through Audits and Confidential Enqui- However, there remains considerable Received 14 April 2020 Revised 7 May 2020 ries across the UK (MBRRACE-UK),­ uncertainty about the burden of disease Accepted 14 May 2020 for neonatal deaths and stillbirths, and in higher-­risk groups, such as neonates, Published Online First 14 June 2020 Public Health England (PHE), Health especially those born preterm, the wider Protection Scotland, Public Health Wales impact of COVID-19 in pregnancy on Arch Dis Child Fetal Neonatal Ed 2020;105:F346– and the Health and Social Care Public neonatal outcomes and the influence F347. doi:10.1136/fetalneonatal-2020-319372 copyright. Health Agency in Northern Ireland. To of different models of postnatal care ORCID iDs limit reporting burden during a period on neonatal disease. Active surveillance Chris Gale http://orcid.​ ​org/0000-​ ​0003-0707-​ ​876X of increased healthcare activity and to through established national systems Marian Knight http://orcid.​ ​org/0000-​ ​0002-1984-​ ​4575 further ensure complete case ascertain- such as the BPSU and UKOSS with very Elizabeth S Draper http://orcid.​ ​org/0000-​ ​0001-9340-​ ​ ment, this BPSU surveillance will also high population-­based case ascertain- 8176 link with routinely recorded neonatal ment is among the simplest, quickest and and paediatric intensive care data held most efficient way to obtain the accurate References in the National Neonatal Research Data- population level incidence data and to 1 Zeng L, Xia S, Yuan W, et al. Neonatal early-­onset infection with SARS-CoV­ -2 in 33 neonates born to base (NNRD) and the Paediatric Inten- determine true infection rates, clinical mothers with COVID-19 in Wuhan, China. JAMA Pediatr sive Care Audit Network (PICANet). The characteristics and outcomes, which are 2020. doi:10.1001/jamapediatrics.2020.0878. [Epub resulting UK population-­level incidence needed to inform optimal perinatal and ahead of print: 26 Mar 2020]. data will be used to inform clinical care, neonatal care. 2 Zeng H, Xu C, Fan J, et al. Antibodies in infants born to mothers with COVID-19 pneumonia. JAMA 2020.

advice to pregnant women and service http://fn.bmj.com/ doi:10.1001/jama.2020.4861. [Epub ahead of print: 26 Twitter Chris Gale @DrCGale, Marian Knight @ provision, and will be shared with global Mar 2020]. Marianfknight, Shamez Ladhani @shamezladhani and registries for international comparisons, 3 Kimberlin DW, Stagno S. Can SARS-­CoV-2 infection be Helen Mactier @HMactier further reducing reporting burden for acquired in utero?: more definitive evidence is needed. clinicians. Collaborators Members of Neonatal complications of JAMA 2020. doi:10.1001/jama.2020.4868. [Epub COVID-19 surveillance group. The BPSU surveillance focuses on ahead of print: 26 Mar 2020]. 4 Liu W, Zhang Q, Chen J, et al. Detection of Covid-19 in symptomatic cases that require hospital Contributors All authors conceived the manuscript. CG drafted the initial version, and all authors children in early January 2020 in Wuhan, China. N Engl on October 2, 2021 by guest. Protected admission and the neonatal impact of contributed to subsequent drafts and reviewed the final J Med 2020;382:1370–1. maternal COVID-19. Similar surveillance version. 5 Dong Y, Mo X, Hu Y, et al. Epidemiology of COVID-19 of children older than 28 days of age who among children in China. Pediatrics 2020:e20200702. Funding The authors have not declared a specific 6 Sutton D, Fuchs K, D’Alton M, et al. Universal screening test positive for SARS-­CoV-2 is being grant for this research from any funding agency in the for SARS-­CoV-2 in women admitted for delivery. N Engl undertaken through PHE, and cases can public, commercial or not-for­ -­profit sectors. J Med 2020. doi:10.1056/NEJMc2009316. [Epub ahead be reported directly to phe.​ ​paedcovid@​ Competing interests All authors are investigators of print: 13 Apr 2020]. nhs.​net. To better understand the vertical on the BPSU Neonatal Complications of COVID-19 7 Zhu H, Wang L, Fang C, et al. Clinical analysis of 10 and horizontal transmission following study. neonates born to mothers with 2019-­nCoV pneumonia. Transl Pediatr 2020;9:51–60. SARS-­CoV-2 infection in pregnancy, Patient consent for publication Not required. 8 Pierce M, Kurinczuk JJ, Spark P, et al. Perinatal outcomes including asymptomatic transmission, the Provenance and peer review Not commissioned; after maternal 2009/H1N1 infection: national cohort periCOVID study (​www.​pericovid.​com) internally peer reviewed. study. BMJ 2011;342:d3214.

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