Progress in Pediatric Cardiology 55 (2019) 101171 Contents lists available at ScienceDirect Progress in Pediatric Cardiology journal homepage: www.elsevier.com/locate/ppedcard Review Neonatal myocardial infarction: A retrospective study and literature review T ⁎ Othman A. Aljohania, , James C. Perrya, Hannah R. El-Sabroutb, Sanjeet R. Hegdea, Jose A. Silva Sepulvedaa, Val A. Catanzaritec, Maryam Tarsad, Amy Kimballe, John W. Moorea, Howaida G. El-Saida a Division of Pediatric Cardiology, Department of Pediatrics, Rady Children's Hospital, University of California, San Diego, CA, United States b Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA, United States c Division of Maternal and Fetal Medicine, Rady Children's Specialists of San Diego, University of California, San Diego, CA, United States d Division of Maternal Fetal Medicine, Department of Reproductive Medicine, University of California, San Diego, CA, United States e Division of Neonatology, Department of Pediatrics, Rady Children's Hospital, University of California, San Diego, CA, United States ARTICLE INFO ABSTRACT Keywords: Neonatal myocardial infarction (MI), in the absence of congenital heart disease or cardiac surgery involving the Neonatal myocardial infarction coronaries, is a rare condition with associated high mortality. A cluster of neonatal myocardial infarction cases Neonatal coronary thrombosis was observed, leading to an investigation of causes and contributors. We performed a single-center review of neonates >37 weeks between 2011 and 2017 to identify neonates with myocardial infarction. Neonates with prior cardiac surgery, congenital anomalies of the coronaries, or sepsis were excluded. Diagnosis of MI was based on ECG changes, elevated troponin, decreased function or regional wall abnormality, and abnormal coronary angiography. There were 4,583 admissions to the NICU without interval changes in referrals or the incidence of neonatal asphyxia. There were six cases of neonatal myocardial infarction. Of 2,155 admissions in the first three years, there were no cases. The incidence in the next three years was 1.3/1,000, 2.7/1,000, and 3.3/1,000. There was a significant difference (0.03, Fishers exact) between the first and second halves of the study period.All cases underwent catheterization, revealing coronary artery thrombosis requiring thrombolytic therapy. Additionally, obstetric providers were surveyed to determine changes in umbilical cord handling practices. Of 48 obstetric providers, 57% changed their practice of cord clamping since 2014: 13% reported cord milking then clamping; 47% delayed cord clamping for a few minutes; 28% delayed cord clamping until the cord stopped pulsating; and 13% immediate clamping. Only 40% reported routine documentation of cord clamping. In con- clusion, there was an increased incidence of neonatal myocardial infarction due to coronary thrombosis. Early diagnosis and initiation of therapy of neonates with myocardial infarction can improve outcomes. A larger study cohort could lead to better understanding of risk factors and outcomes of myocardial infraction in neonates. 1. Introduction hearts are associated with thromboembolism and/or birth asphyxia [1]. In near-term pregnancies, thrombosis of umbilical vessels is not un- Neonatal myocardial infarction (MI) in structurally normal heart common [1,4]. These thrombi have the potential to embolize to the and coronary anatomy is a rare condition with high mortality [1]. There fetus, can compromise fetal circulation, and cause fetal death [4]. have been sporadic reports since the first description in 1947, with In late 2012, the American College of Obstetricians and mortality due to severe MI of 90% [2]. Neonatal MI can be classified Gynecologists (ACOG) released a committee opinion recommending into three types: (1) neonatal MI associated with congenital heart dis- delayed cord clamping (DCC) when feasible for preterm births ease (CHD); (2) neonatal MI after cardiac surgery; and (3) neonatal MI (<32 weeks) and commenting on potential benefits [5]. The American without associated structural/congenital heart disease [3]. Academy of Pediatrics (AAP) endorsed ACOG's recommendations in Most of the reported cases of perinatal MI in structurally normal 2012, and along with the American Heart Association (AHA) changed Abbreviations: MI, myocardial infarction; DCC, delayed cord clamping; CHD, congenital heart disease; ACOG, American College of Obstetricians and Gynecologists; AAP, American Academy of Pediatrics; AHA, American Heart Association; NRP, Neonatal Resuscitation Program; DOL, day of life; echo, echocardiogram; cath, catheterization ⁎ Corresponding author at: 3020 Children's Way, Rady Children's Hospital, San Diego, CA 92123, United States. E-mail address: [email protected] (O.A. Aljohani). https://doi.org/10.1016/j.ppedcard.2019.101171 Received 23 May 2019; Received in revised form 4 October 2019; Accepted 14 October 2019 Available online 19 October 2019 1058-9813/ © 2019 Elsevier B.V. All rights reserved. O.A. Aljohani, et al. Progress in Pediatric Cardiology 55 (2019) 101171 the Neonatal Resuscitation Program (NRP) guidelines in 2015 to re- panel, beta-2 glycoprotein 1 (B2GP1) antibody assay, DRVVT screen commend DCC in “most vigorous term and preterm newborns for at (Lupus anticoagulant), and homocysteine level. least 30-60 seconds”. The World Health Organization recommends a An assessment of changes in umbilical cord handling practices was similar practice. DCC has been associated with increased hemoglobin performed by an online survey of regional obstetric providers. The levels at birth and improved iron store for several months after birth in survey was voluntary, and responses were kept anonymous and con- term infants. For preterm infants, DCC may improve transitional cir- fidential. culation and increase red blood cell volume, reducing the need for blood transfusions, and the incidence of both necrotizing enterocolitis 2.2. Statistical analysis and intraventricular hemorrhage. This practice may increase the risk of jaundice, and appropriate monitoring and access to treatment are re- Categorical variables were summarized as frequencies and percen- commended [6]. Prior to the formal recommendations made by ACOG tages while continuous variables were summarized as medians with and the AAP, there was variable umbilical cord care between obstetric ranges (minimum-maximum). Fisher's exact test was used to compare providers and institutions. The practices include immediate cord the incidence between the first three years (August 2011–July 2014) vs. clamping and variation of milking or stripping of the umbilical cord. the last three years (August 2014–July 2017). Statistical significance Umbilical cord milking has been considered as a means of achieving was defined as P < 0.05. increased placental to newborn transfusion in a rapid time frame of 10–15 s. It has particular appeal for circumstances in which the re- 3. Results commended 30–60 s delay in umbilical cord clamping may be deemed too long, such as when immediate infant resuscitation is needed or During the study period, there were 4,583 admissions to the NICU. maternal hemodynamic instability occurs. Currently, ACOG and the There were no changes in the referral region, incidence of neonatal AAP have stated there is insufficient evidence to either support or refute asphyxia among admissions, or changes in the diagnostic criteria for umbilical cord milking in term or preterm infants [7]. neonatal MI. Demographics and clinical data are summarized in Tables In 2017, Molkara et al. reported three cases of neonatal MI and 1 and 2. Out of 2,155 admissions in the first three years between Aug proposed a treatment algorithm using tissue plasminogen activator 2011 and Jul 2014, no cases were identified. The incidence increased in (tPA) at our institution [8]. Since that report, there have been three the following three years: 1.3 cases per 1,000 (1 case in 743 admis- additional cases, prompting a retrospective review study to assess both sions); 2.7 cases per 1,000 (2 cases in 784 admissions); and 3.3 cases the incidence of neonatal MI and potential contributing factors (from per 1,000 (3 cases in 901 admissions). There was a statistically sig- 2011 to 2017). We hypothesized that the incidence of neonatal MI had nificant difference between the first and second halves ofthestudy increased in recent years. The study included an online survey of re- period (P-value of 0.03 using Fisher's exact test (0/2,155 admissions vs. gional obstetric providers to assess changes in umbilical cord handling 6/2,428 admissions). Two patients had identifiable risk factors; one practices. patient had a history of birth asphyxia requiring cooling, and the other patient had complex CHD [infradiaphragmatic total anomalous pul- 2. Material and methods monary venous connection (TAPVC)]. All six cases underwent cardiac catheterization and were found to have coronary thrombosis requiring 2.1. Study design and population thrombolytic therapy. Out of five patients who presented with re- spiratory distress, four had abnormal troponin levels and ECGs, and all The Institutional Review Board of Rady Children's Hospital of San had abnormal echocardiograms. Diego (RCHSD) approved the retrospective chart review study and The online survey was sent to obstetric care providers who were questionnaire. RCHSD is a tertiary referral center serving San Diego, members of a regional perinatal CME group