Coronary artery dilatation in neonates: A novel case series

Introduction

Coronary artery dilatation (CAD) is defined as focal or diffuse enlargement of a coronary artery segment exceeding 150% of the adjacent normal segment diameter. ¹ CAD is well recognized in Kawasaki disease and multisystem inflammatory syndrome in children (MIS-C) and in the conditions characterized by systemic inflammation and immune-mediated vascular injury.^2–4 However, CAD in the neonatal period remains infrequently reported, despite reports of multisystem inflammatory syndrome in neonates (MIS-N) during the COVID-19 pandemic. MIS-N was defined 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. ⁵ Emerging data suggest that maternal SARS-CoV-2 infection during antenatal period and antibody transfer, as well as maternal comorbidities such as preeclampsia and gestational diabetes, may predispose neonates to inflammatory endothelial injury.^6–8 Maternal antibodies following COVID-19 vaccination can also pass trans placentally. Whether neonatal CAD represents a transient post-inflammatory phenomenon or a marker of severe systemic illness remains uncertain, as does the need for treatment in asymptomatic cases.

Although MIS-N received attention during the COVID-19 pandemic, data on long-term outcomes and follow-up of neonates with CAD are limited. This case series describes the clinical profile and short-term outcomes of neonates with CAD admitted to a tertiary-care neonatal intensive care unit.

Materials and methods

This retrospective, record-based case series was conducted in the neonatal intensive care unit (NICU) of a Government Medical College in South India. All neonates (both inborn and out born) who were admitted in NICU over a 2-year period (January 2023 to December 2024) with echo cardio graphically confirmed CAD were included. CAD was defined as a coronary artery Z-score >2. Gender-specific, body surface area adjusted z-scores of internal diameter of the proximal coronary arteries (LMCA, LAD, LCX, RCA) were calculated based on Lambda-Mu-Sigma method by software. ⁹ Two well experienced pediatric cardiologists were doing the echo cardio grapy for the suspected cardiac cases. The neonatology resident was doing bedside ECHO for all the sick neonates during an emergency situation if cardiologist was not available. Video of the echocardiography was then sent to the cardiologist through WhatsApp and the cardiologist used to repeat the ECHO next day in all suspected cases.

Maternal history, neonatal clinical features, working diagnosis, laboratory parameters, echocardiographic findings, treatments, and outcomes were extracted from hospital records and follow-up files. Working diagnosis were assigned based on clinical course and laboratory parameters. The diagnosis of MIS-N was established according to the published criteria, as summarized in Table 1. ¹⁰

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Table 1.

Criteria for neonatal multisystem inflammatory syndrome (MIS-N) secondary to maternal SARS-CoV-2 exposure or infection.

1. A neonate <28 days at the time of presentation

2. Lab or epidemiological evidence of SARS-CoV-2 infection in the mother.

i. Positive SARS-CoV-2 testing in pregnancy (RT-PCR/serology/Antigen)

ii. Symptoms consistent with SARS-CoV-2 infection in pregnancy

iii. Serological evidence in the neonate (Positive IgG).

3. Clinical criteria

Severe illness needing hospitalization AND

≥2 organ systems affected (Cardiac, renal, hematologic, gastrointestinal, dermatologic, neurological, temperature instability) OR

Cardiac AV conduction abnormalities OR coronary dilatation or aneurysm

4. Laboratory evidence of inflammation

One or more of the following: An elevated CRP, ESR, LDH, fibrinogen, D-dimer, IL-6,

Procalcitonin, ferritin, elevated neutrophils or reduced lymphocytes, low albumin.

5. No alternate diagnosis (such as birth asphyxia-cord pH≤ 7.0 and Apgar score ≤3 at 5 min; viral or bacterial sepsis-confirmed blood culture; maternal lupus causing conduction abnormalities)

Results

A total of 24 neonates with CAD were identified during the study period from the monthly statistical report. The mean gestational age was 35.5 (2.2) weeks and mean birth weight was 2557 g (646 g). Majority were preterm (70.8%, n = 17) and of whom 54.2% (n = 13) were late preterm. There was no gender predominance (54.2% males). Nine neonates (37.5%) were delivered by lower segment cesarean section. Maternal diabetes was present in 37.5% (n = 9) and pregnancy-induced hypertension in 54.2% (n = 13). A history suggestive of antenatal viral illness was reported in 29.2% (n = 7) of mothers. Three neonates (12.5%) required resuscitation at birth. All mothers had received COVID-19 vaccination.

Respiratory distress was the most common presenting symptom, observed in 95.8% (n = 23) of neonates; one infant presented with fever from day 1 of life. Invasive ventilation was required in 79.1% (n = 19). The working diagnoses at admission included respiratory distress syndrome (RDS) (45.8%), congenital pneumonia (29.2%), sepsis (16.7%), meconium aspiration syndrome (4.1%), and perinatal asphyxia (4.1%). Shock requiring inotropic support developed in 75% (n = 18) during the course of illness. Hepatosplenomegaly was noted in 20.5% (n = 5). Echocardiography was performed for various clinical indications. CAD was detected incidentally during echocardiography which was performed to evaluate persistent pulmonary hypertension of the newborn (PPHN), assess ventricular dysfunction during shock, and exclude congenital heart disease, particularly in those with an unexpected clinical course.

MIS-N subgroup

One-third of the cohort (n = 8) fulfilled diagnostic criteria of MIS-N (Table 1). Among these, three representative cases are summarized below.

The first was a term male neonate (birth weight 3100 g) referred on day 2 of life with fever from day 1, without any other symptoms. Initial evaluation suggested suspected sepsis; however, cultures and cerebrospinal fluid analysis were normal, and fever persisted beyond day 5. Echocardiography performed to exclude infective endocarditis revealed left main coronary artery (LMCA) dilatation (1.8 mm). Secondary inflammatory markers were markedly elevated (Serum ferritin level 1650 mcg/L, fibrinogen level 132 mg/dl, LDH level 1914 U/L, D-dimer 2.8 mcg/ml and pro-BNP of >35,000 pg/ml). Maternal and neonatal COVID-19 IgG were positive. A diagnosis of MIS-N was made, and treatment with intravenous immunoglobulin (IVIG, 2 g/kg over 2 days) and intravenous methylprednisolone was initiated as per the treatment protocol of MIS-N. Fever subsided after the first IVIG dose, LMCA size reduced within 1 week, and coronary dimensions normalized by 3 months while on follow-up.

The second case was a late preterm female neonate (35 weeks, 2100 g) with respiratory distress from birth. She was initially managed as congenital pneumonia. Baby was referred to this hospital on day 6 in view of multiple extubation failures. Initial ECHO at admission was normal. As the baby was progressing to features of chronic lung disease, echocardiography was repeated at 3rd week of life and revealed dilatation of the right, and left main coronary arteries. Inflammatory markers supported MIS-N, and the infant responded to IVIG followed by methylprednisolone, with successful extubation shortly thereafter. Aspirin was continued for a short period, till normalization of coronaries.

The third case was a late preterm neonate (35 weeks, 2100 g) who initially presented with mild respiratory distress on day 1 but subsequently developed encephalopathy and compensated shock on day 2. Sepsis evaluation was negative. Echocardiography revealed CAD on second day (Figures 1 and 2 ). Inflammatory markers were favoring the criteria for MIS-N and the infant showed a dramatic clinical response to IVIG. Shock was corrected on the very next day. Baby was given corticosteroids and aspirin. Coronary dimensions normalized on follow-up between 3 and 6 months.

The rest of the five babies have almost similar clinical course. They presented with features of RDS or congenital pneumonia needing either NIV or invasive ventilation. As they developed shock, ECHO was done and incidentally detected CAD. Among the MIS-N group, three infants had severe pulmonary arterial hypertension (PAH), two had moderate PAH, two had mild PAH, and one had no PAH. Left ventricular ejection fraction was <55% in 75% of cases. Aspirin was continued at discharge in 87.5% (n = 7). All infants with MIS-N survived to discharge, and all had complete resolution of coronary dilatation by 3–6 months.

For those who have satisfied the clinical criteria of MIS-N, therapy was done as per MIS-N treatment guidelines. IVIG was given at 2 gm/kg as single or two divided doses over 2 days. Then intravenous methyl prednisolone was given at 1–2 mg/kg/day as two divided doses, followed by oral prednisolone to get it tapered over 2–3 weeks. Aspirin was given at 3–5 mg/kg/day once daily after steroids or along with steroids depending on the opinion from cardiologist. It was continued for 6–8 weeks or till the resolution of coronary abnormalities as per cardiologist’s advice.OPEN IN VIEWER

Figure 1.

Echocardiographic images showing severe left main coronary artery dilatation (LMCA) with proximal diameter 2.07 mm (bigger arrow) and distal diameter as 1.32 mm (small arrow) before giving IVIG and steroids.

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Figure 2.

Echocardiographic images of same patient shown in Figure 1 shows significant decrease in diameter (1.23 mm) of LMCA after 1 week of receiving IVIG and steroids.

Echocardiographic and laboratory findings

Echocardiographic findings are summarized in Table 2. Left main coronary artery dilatation was present in 100% of neonates with MIS-N. At discharge, coronary dilatation persisted in 11.1% (n = 2) with right coronary artery involvement and 16.6% (n = 3) with LMCA involvement; all resolved between 3 and 6 months.

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Table 2.

Comparison of secondary inflammatory markers between MIS-N and other cases.

​	MIS-N (n = 8)	Other diagnosis (n = 16)
D-dimer a	4 tested—all positive	Not tested
LDH b	7 tested—all positive	9 tested—all positive
Pro-BNP c	4 tested—all positive	2 tested—both positive
Ferritin d	All were positive	9/16 were positive
Fibrinogen e	Was not elevated in any.	Was not elevated in any
CRP	All negative	7/16 were positive

^aD-dimer 0–0.5 mcg/ml.

^bLDH- 125–220 U/L.

^cpro-BNP- – 0–300 pg/ml.

^dFerritin- 20–260 mcg/L.

^eFibrinogen- 200–400 mg/dl.

Inflammatory marker patterns are summarized in Table 3. Fibrinogen was not elevated in any case. Lactate dehydrogenase, D-dimer, and pro–B-type natriuretic peptide were elevated in all tested neonates. C-reactive protein was negative in all except one MIS-N case. Among the 17 neonates in whom secondary inflammatory markers were assessed, 94.1% (n = 16) had elevation of two or more markers. All tested mother–infant pairs (n = 11) had positive COVID-19 antibodies, while all neonates tested negative for COVID-19 antigen. Limited availability of testing restricted complete evaluation in all cases.

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Table 3.

Comparison of coronaries affected between MIS-N and other causes.

​	MIS-N (%) n = 8	Other aetiologies (%) n = 16
RCA	25%	62.5%
LMCA	100%	75%
LCA	62.5%	68.75%
LAD	37.5%	50%

RCA—Right coronary artery, LMCA—Left main coronary artery, LCA—Left circumflex artery, LAD—Left anterior descending artery.

Discussion

This case series highlights coronary artery dilatation (CAD) as an important and often under-recognized finding in critically ill neonates. One-third of cases were attributable to MIS-N, while the remainder were attributed to other inflammatory or critical illness states, suggesting that CAD may represent a transient post-inflammatory vascular change. Whether CAD represents a marker of illness severity may need further comparative studies. Approximately half of the affected neonates were late preterm, emphasizing the vulnerability of this subgroup.

Respiratory distress was the predominant presenting feature, and the majority of neonates developed shock requiring inotropic support. In late preterm neonates with poorly responsive respiratory distress and shock, targeted evaluation of the coronary arteries may provide a critical diagnostic clue. In one notable case, a neonate with presumed congenital pneumonia and PPHN who remained ventilator-dependent into the third week of life showed a dramatic clinical response to IVIG after CAD prompted consideration of MIS-N; this infant also had a coronary aneurysm and responded despite delayed initiation of immunomodulatory therapy. Although fever is not a mandatory criterion for MIS-N, unexplained or persistent fever should raise suspicion and prompt evaluation in appropriate clinical contexts.

Inflammatory marker patterns in this cohort highlight important diagnostic challenges. Fibrinogen levels were not elevated in any case, while LDH, D-dimer, and pro-BNP were frequently elevated, and CRP was largely negative. Given that many biochemical markers are nonspecifically elevated in critically ill neonates and that optimal neonatal cut-offs—particularly in preterm infants—are not well established, these markers may have limited discriminatory value for MIS-N. Consequently, clinical course and echocardiographic findings may be more reliable for diagnosis. In the post–COVID-19 vaccination era, universal maternal–infant antibody positivity further limits the utility of serology in distinguishing MIS-N from other inflammatory conditions.

Consistent with observations in Kawasaki disease and MIS-C, coronary dilatation in our cohort resolved completely within months. Prior pediatric studies attribute coronary involvement in hyperinflammatory states to cytokine-mediated endothelial injury and immune complex deposition. Our findings extend this paradigm to the neonatal period, potentially influenced by antenatal inflammation, maternal SARS-CoV-2 exposure, antibody transfer, or vaccination. Whether neonatal CAD represents a distinct Kawasaki-like process, infection-related inflammation, or a COVID-19-associated immune phenomenon remains unresolved. The need for immunomodulatory therapy with IVIG and steroids also may need expert discussion on case to case basis.

A key therapeutic implication of this study is the potential role of early immunomodulation. IVIG, with or without corticosteroids, appeared beneficial in neonates with MIS-N, CAD, shock, or myocardial dysfunction, paralleling treatment strategies in Kawasaki disease and MIS-C. Aspirin and corticosteroids were used selectively. Importantly, all neonates underwent echocardiographic follow-up through discharge and up to 6 months, confirming complete resolution of coronary abnormalities.

The study is limited by its retrospective design, small sample size, lack of a control group, incomplete availability of inflammatory and virological testing due to resource constraints and absence of long-term follow-up. Additionally, the relative contribution of maternal infection versus vaccination to neonatal antibody positivity could not be delineated.

Whether IVIG is beneficial in neonates with CAD who do not meet MIS-N criteria warrants further investigation. Larger, multicenter studies are needed to define the prognostic value of CAD and guide immunomodulatory therapy in this population.

Conclusion

Coronary artery dilatation should be actively searched in critically ill neonates with an atypical clinical course, poor response to conventional management, or sepsis-like presentation without supportive laboratory evidence. MIS-N should be considered, particularly in late preterm neonates presenting with respiratory distress and shock. However, not all cases of coronary dilatation represent MIS-N, and lack of response to immunomodulatory therapy should prompt reconsideration of the diagnosis. Secondary inflammatory markers have limited discriminatory value in neonates, whereas echocardiographic findings may provide an important diagnostic clue. Bedside echocardiography thus plays a crucial role in the evaluation and management of sick neonates in the post–COVID-19 era.