Multisystem inflammatory syndrome in neonates (MIS-N): a systematic review

Abstract

Recently, a new pattern of multisystem inflammatory syndrome following an infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged globally. The initial cases were described in the adult population followed by sporadic cases in the pediatric population also. By the end of 2020, similar reports were recognised in the neonatal age group. The purpose of this study was to systematically review clinical characteristics, laboratory parameters, treatment, and outcomes of neonates with multisystem inflammatory syndrome in neonates (MIS-N). A systematic review was conducted after registering with PROSPERO and electronic databases including MEDLINE, EMBASE, PubMed, SCOPUS, Google Scholar, and Web of Science were searched from January 1st 2020 till September 30th 2022. A total of 27 studies describing 104 neonates were analysed. The mean gestation age and birth weight was 35.9 ± 3.3 weeks and 2255.7 ± 783.7 g respectively. A large proportion (91.3%) of the reported cases belonged to the South-East Asian region. The median age of presentation was 2 days (range: 1–28 days) with cardiovascular system being the predominant system involved in 83.65% followed by respiratory (64.42%). Fever was noted in only 20.2%. Commonly elevated inflammatory markers were IL-6 in 86.7% and D-dimer in 81.1%. Echocardiographic evaluation suggested ventricular dysfunction in 35.8% and dilated coronary arteries in 28.3%. Evidence of SARS-CoV-2 antibodies (IgG or IgM) was seen in 95.9% neonates and evidence of maternal SARS-CoV-2 infection, either as history of COVID infection or positive antigen or antibody test, was noted in 100% of the cases. Early MIS-N was reported in 58 (55.8%) cases, late MIS-N in 28 (26.9%), and 18 cases (17.3%) did not report the timing of presentation. There was a statistically increased proportion of preterm infants (67.2%, p < 0.001), and a trend towards increased low birth weight infants, in the early MIS-N group when compared to the infants with late MIS-N. Fever (39.3%), central nervous system (50%), and gastrointestinal manifestations (57.1%) were significantly higher in the late MIS-N group ( p = 0.03, 0.02, 0.01 respectively). The anti-inflammatory agents used for the treatment of MIS-N included steroids 80.8% which were given for a median of 10 (range 3–35) days and IVIg in 79.2% with a median of 2 (range 1–5) doses. The outcomes were available for 98 cases, of whom 8 (8.2%) died during treatment in hospital and 90 (91.8%) were successfully discharged home. Conclusion : MIS-N has a predilection for late preterm males with predominant cardiovascular involvement. The diagnosis is challenging in neonatal period due to overlap with neonatal morbidities and a high risk of suspicion is warranted, especially in presence of supportive maternal and neonatal clinical history. The major limitation of the review was inclusion of case reports and case series, and highlights need of global registries for MIS-N. ...

Multisystem inflammatory syndrome in neonates (MIS-N) associated with perinatal SARS CoV-2 infection: Does it exist?

“…Hence, we propose a definition of MIS-N based on revised CDC criteria utilizing information from different case series and systematic reviews [ 11 , 14 , 15 , 17 , 18 ]. [ 12 ].

Figure 1 Revised 2023 Council of State and Territorial Epidemiologists (CSTE) and CDC Surveillance Case definition of MIS-C (see table 1 for details).

…”

“…Unusual findings that cannot be otherwise explained such as profound ventricular dysfunction, atrioventricular conduction abnormalities, intracardiac thrombus or coronary dilation or aneurysm, and non-immune hydrops increase the index of suspicion for MIS-N ( Figure 3 ).

Figure 3 Manifestations of Multisystem inflammatory syndrome in neonates (MIS-N) secondary to maternal COVID-19 infection (based on a systematic review by Shaiba et al [ 11 ] Mascarenhas et al [ 12 ] and Ramaswamy et al [ 13 ] Copyright Satyan Lakshminrusimha

…”

“… Manifestations of Multisystem inflammatory syndrome in neonates (MIS-N) secondary to maternal COVID-19 infection (based on a systematic review by Shaiba et al [ 11 ] Mascarenhas et al [ 12 ] and Ramaswamy et al [ 13 ] Copyright Satyan Lakshminrusimha …”

“…Diagnostic criteria have been suggested for MIS-N as an inflammatory syndrome in neonates following birth to mothers with SARS-CoV-2 infection during late pregnancy or secondary to neonatal SARS CoV-2 infection [ 10 ]. Case reports from India, US, Mexico, Saudi Arabia, Iran, Brazil, Israel, Netherlands and Qatar meeting similar criteria for MIS-N were published and three systematic reviews have compiled data from 47, 104 and 48 infants have been published [ [11] , [12] , [13] ]. Majority of patients including two of the largest case series have reported from India and include neonates with unusual presentations such as arrhythmias including atrioventricular block, cardiac dysfunction, dilated coronary arteries, skin desquamation, enterocolitis, and pneumonia-like changes on chest X-ray [ 14 , 15 ].…”

Neonatal COVID-19 – The past, present and the future

“…Ramaswamy et al provide us with an updated systematic review with information from 58 patients presenting with MIS-N [ 15 ]. A review of 104 patients that included 41 “possible” and 8 “unlikely” MIS-N cases was recently published [ 16 ]. It is concerning that these neonates have a high mortality rate (8-11%) compared to MIS-C in children as reported by the Centers for Disease Control and Prevention (CDC, 76 deaths/9370 cases – 0.8% - accessed on March 26, 2023) [ 12 ].…”