Clozapine induced neonatal right ventricular noncompaction cardiomyopathy：A case report

Clozapine induced neonatal right ventricular noncompaction cardiomyopathy：A case report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Clozapine induced neonatal right ventricular noncompaction cardiomyopathy：A case report Yang Wen, Han Wang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7735073/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Clozapine is an atypical antipsychotic indicated for treatment-resistant schizophrenia.It is associated with severe cardiac adverse events including myocarditis and cardiomyopathy. We report a case of a neonate who developed right ventricular noncompaction cardiomyopathy (RVNC) after birth and eventually died of right heart failure. Her mother had been taking clozapine during pregnancy and lactation. We suspect clozapine is responsible for her cardiomyopathy. Figures Figure 1 Background Clozapine is an antipsychotic which always used in treatment-resistant schizophrenia and can reduce suicide rate for the patients [ 1 ]. It is associated with severe cardiac complications including myocarditis and cardiomyopathy in psychotic patients[ 2 ]. Left ventricular noncompaction cardiomyopathy (LVNC) has been reported in patient with chronic clozapine use [ 3 ]. However, the safety data of clozapine use during pregnancy and lactation are very limited. Clozapine can cross the placental barrier, decreased fetal heart rate variability and absence of accelerations have been found in previous cases[ 4 , 5 , 6 ]. Neonatal cardiomyopathy induced by clozapine has not been reported before. The case we report may increase the safety data of clozapine during pregnancy and lactation. Case presentation A premature neonate at 35 + 5 weeks gestation was delivered by caesarean section due to abnormal fetal fetal heart rate (FHR) in local hospital. Her mother had been taking clozapine 250mg during pregnancy because of schizophrenia. FHR monitoring has been suggestive slow since 30 weeks gestation. Abnormal myocardial injury markers and neonatal pneumonia was found after she was born. Her symptom improved after 9 days of treatment with sodium creatine phosphate, high doses of vitamin C and SULPERAZON. However, 25 days later, she developed poor response and milk consumption decreased by 1/3. Then she was admitted to our hospital. We learned that after she was discharged from the hospital, her mother was still taking clozapine and breast-feeding her. We told the mother to stop breastfeeding. On the second day, Myocardial injury markers were significantly increased with NT-probNP 14011.7pg/ mL. CTnI 14.57ng/ml and CK-MB 71.29ng/ml. Echocardiography showed the right ventricle (RV) increased to 5.9mm in anteroposterior diameter. The density of muscle wall, septum and outflow tract of RV increased widely. Right ventricular systolic and diastolic function reduced, but left ventricular systolic function was in the normal range. At that time, extensive myocardial calcification was considered. Electrolyte test showed serum calcium, magnesium, phosphorus was 2.15mmol/L, 0.84mmol/L, 3.35mmol/L respectively. Parathyroid hormone and vitamin D were normal. No calcium deposits in other organs were found by ultrasound in liver, gallbladder, spleen and brain. Tandem mass spectrometry was examined at an out-of-hospital facility, showed genetic metabolites no abnormalities. We considered that the small possibility of myocardial calcification caused by abnormal calcium, phosphorus metabolism and genetic metabolism. Creatine phosphate sodium, spironolactone, hydrochlorothiazide, and supportive therapy inciuding non-invasive ventilator, oxygen inhalation, warmth, sputum aspiration, nutrition were given, but no improvement, her right atria (RA) and RV were progressively dilated in a few short days, On day 5, the myocardium of the RV was thickened, especially free wall. Sinusoidal changes were seen at the apex of the RV, and the motion of the wall was obviously weakened. Captopril, milrinone and dobutamine were subsequently added, but can't reverse the conditions. Aditionally, we pursued evidence of viral infection, all the antibodies of EB virus, coxsackie virus, rubella virus, cytomegalovirus, herpes simplex virus and toxoplasma were negative. Antinuclear antibody line analysis showed no abnormalities too. The whole exome sequencing(WES) of the child and her parents did not find pathogenic or suspected pathogenic variants that clearly explained the her phenotype. However, Some variants defined as "variant of uncertain significance(VUS)" in the American College of Medical Genetics(ACMG) rating were detected, including AGXT, ARHGAP31,EYA4, FLT4, NCACNA1D, KMT2D and SCN5A (Table 1). On the 13th day of admission, the anteroposterior diameter of RV dilated to 14mm, while the RA dilated to 23*18mm. Non-compact layer: compact layer > 2. The echo of interventricular septum was uneven and strip-shaped. Echocardiography study showed prominent trabecular meshwork with deep intert rabecular recesses in the RV apex. Color flow Doppler examination confirmed the presence of blood flow within the trabeculae. Neither apical segment nor RV wall had obvious pulse, ventricular septal pulse stiff. It was seen that change rate of RV area was less than 10%. The LV become a D shape oppressed by augmented right heart. RVNC was diagnosed. Percutaneous oxygen saturation can only be maintained at 80–85% even with invasive respiratory support (FiO2 100%), and accompanied by shortness of breath, obvious dyspnea, increased heart rate (160–170 beats/min), poor response. The family eventually abandoned all treatment. Discussion and conclusions According to national databases reporting adverse drug effects, the rate of cardiomyopathy in clozapine treated patients in the U.S. was 8.9 per 100,000 person-years[ 7 ]. The Australian population has a higher incidence, Youssef DL et al[ 8 ]evaluated 129 Australia patients initiated on clozapine, analysed the incidence of clozapine-induced myocarditis and cardiomyopathy was 3.88% and 4.65% respectively. A systematic review of the literature on cardiomyopathy associated with clozapine concluded that symptoms developed at an average of 14.4 months after initiating clozapine. The clinical presentation was generally consistent with heart failure, including shortness of breath (60%) and palpitations (36%). Echocardiography showed dilated cardiomyopathy in 39% of cases and was not specified in other cases[ 2 ]. In the reported cases of clozapine induced cardiotoxicity, the most common manifestations were reduced LVEF, left heart dilation and LVNC[ 3 , 9 ]. However, our case presented with RVNC and right heart failure absence of reduction in LVEF and other coexisting cardiac abnormalities (Fig. 1 ). Ventricular noncompaction typically displays a dense trabecular meshwork with deep intertrabecular recesses, with the most commonly involved site being the LV and the RV only in a paucity of cases[ 10 ]. The pathogenesis of ventricular noncompaction is still unclear. Recent studies have revealed that gene mutation is an important etiology[ 11 ]. However, all the variants for the child were accessed as AUS by ACMG rating. The genetic mode of the variants were autosomal dominant(AD) except for AGXT, but AGXT-related disease is primary hyperoxaluria type 1, which does not match the phenotype of the child. Furthermore, the parents denied genetic and metabolic disease and had no associated clinical manifestations. Therefore, We considered that none of these might be pathogenic genes. Clozapine can cross the placental barrier as well as breast milk[ 12 ], there have been cases of foetuses exposed to clozapine who have demonstrated decreased heart rate variability[ 4 , 5 , 6 ]. Sedation and adverse hematologic effects have been reported during lactation[ 13 ]. However, neonatal cardiomyopathy exposed to clozapine during pregnancy and lactation has not been reported. Schoretsanitis G et al[ 12 ] reviewed the concentrations of antipsychotics in maternal blood (serum or plasma), amniotic fluid, umbilical cord blood, and/or breast milk. The penetration ratios of clozapine for amniotic fluid, umbilical cord blood, and breast milk to maternal blood ranged 0.31–0.82, 0.39–0.58, 2.79–4.32 respectively. Noteworthily, the concentration of clozapine in breast milk was several times that of the maternal blood. In our case, the mother took clozapine until 29 days after the baby birth. FHR(fetal heart rate) monitoring consistently suggested slow since 30 weeks gestation in utero. At birth, myocardial injury markers was significantly increased, then the infant were breastfed for more than 20 days. There was no obvious intrauterine infection observed, and no abnormality found in the screening of immune and metabolic diseases. Therefore, we considered that passive exposure to clozapine during both pregnancy and lactation may have contributed to the outcome of the infant. In conclusion, taking clozapine during pregnancy or lactation may cause cardiomyopathy for fetus and neonate. Although the mechanism is unclear for the neonatal ventricular noncompaction caused by clozapine, it reminds us that fetal monitor may need to be more frequent and breastfeeding is better to avoid when clozapine must be taken. Declarations Funding This research did not receive any specifc Grant from funding agencies in the public, commercial, or not-for-proft sectors. Consent Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Competing interests The authors declare that they have no competing interests. Acknowledgements We would like to thanks the patient and her family for giving us permission to publish this case report. Author Contribution Yang Wen and Han Wang are the researchers of the article, and Yang Wen 's contribution provides credit and assumes responsibility. Han Wang provided information search and contributed partially to the writing of the article. References Hennen J, Baldessarini RJ (2005) Suicidal risk during treatment with clozapine: a meta-analysis. Schizophr Res 73(2):139–145 Alawami M, Wasywich C, Cicovic A, Kenedi C. A systematic review of clozapine induced cardiomyopathy. Int J Cardiol. 2014 Sep 20;176(2):315-20. doi: 10.1016/j.ijcard.2014.07.103. Finsterer J, Stöllberger C. Noncompaction and Dilated Cardiomyopathy in a Patient with Schizophrenia. Case Rep Cardiol. 2016;2016:7384264. doi: 10.1155/2016/7384264. Epub 2016 Jul 31. Guyon L, Auffret M, Coussemacq M, Béné J, Deruelle P, Gautier S (2015) Alteration of the fetal heart rate pattern induced by the use of clozapine during pregnancy. Therapie 70(3):301–303 Yogev Y, Ben-Haroush A, Kaplan B (2002) Maternal clozapine treatment and decreased fetal heart rate variability. Int J Gynecol Obstet 79(3):259–260. Novikova N, Chitnis M, Linder V, Hofmeyr GJ. Atypical antipsychotic (clozapine) self-poisoning in late pregnancy presenting with absent fetal heart rate variability without acidosis and delayed peristalsis in the newborn baby: a case report. Aust N Z J Obstet Gynaecol. 2009 Aug;49(4):442-4. doi: 10.1111/j.1479-828X.2009.01017.x. La Grenade L, Graham D, Trontell A. Myocarditis and cardiomyopathy associated with clozapine use in the United States. N Engl J Med Jul 19 2001;345(3):224–5. Youssef DL, Narayanan P, Gill N. Incidence and risk factors for clozapine-induced myocarditis and cardiomyopathy at a regional mental health service in Australia. Australas Psychiatry. 2016 Apr;24(2):176-80. doi: 10.1177/1039856215604480. Bellissima BL, Tingle MD, Cicović A, Alawami M, Kenedi C. A systematic review of clozapine-induced myocarditis. Int J Cardiol. 2018 May 15;259:122-129. doi: 10.1016/j.ijcard.2017.12.102. Bekheit S, Karam B, Daneshvar F, Zaidan J, Tabet R, Spagnola J, Lafferty J. Sudden cardiac death in isolated right ventricular hypertrabeculation/noncompaction cardiomyopathy. Ann Noninvasive Electrocardiol. 2018 Jul;23(4):e12487. doi: 10.1111/anec.12487. van Waning JI, Moesker J, Heijsman D, Boersma E, Majoor-Krakauer D. Systematic Review of Genotype-Phenotype Correlations in Noncompaction Cardiomyopathy. J Am Heart Assoc. 2019 Dec 3;8(23):e012993. doi: 10.1161/JAHA.119.012993. Schoretsanitis G, Westin AA, Deligiannidis KM, Spigset O, Paulzen M. Excretion of Antipsychotics Into the Amniotic Fluid, Umbilical Cord Blood, and Breast Milk: A Systematic Critical Review and Combined Analysis. Ther Drug Monit. 2020 Apr;42(2):245-254. doi: 10.1097/FTD.0000000000000692. https://www.e-lactancia.org/breastfeeding/clozapine/product/ Additional Declarations No competing interests reported. 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1","display":"","copyAsset":false,"role":"figure","size":490565,"visible":true,"origin":"","legend":"\u003cp\u003eshows echocardiography, A shows the baby is 26 day,the arrow area not found prominent trabecular meshwork with deep intert rabecular recesses in the RV apex;B shows the baby is 30 day,B1 shows the compacted layer is 1mm,B2 shows the uncompacted layer is 6.3mm;C shows the baby is 33 day,the arrow area found obvious prominent trabecular meshwork with deep intert rabecular recesses in the RV apex;D shows the baby is 38 day ,D1 shows the RV anteroposterior diameter size is 13.8mm;D2 shows the arrow area can found prominent trabecular meshwork with deep intert rabecular recesses in the RV apex;D3 shows RV apical short axis section,that shows Color flow Doppler examination confirmed the presence of blood flow within the trabeculae,D4 shows RV apical short axis section,that shows the arrow area can found prominent trabecular meshwork with deep intert rabecular recesses in the RV apex.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7735073/v1/9b597d3d4d8b9f616da6aa89.png"},{"id":103505332,"identity":"ef1010a0-d8c9-472f-9a97-7c1f1062da06","added_by":"auto","created_at":"2026-02-26 13:30:02","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":789896,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7735073/v1/b5f18e0d-28ac-435f-8648-a4fcb5e7a4ae.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clozapine induced neonatal right ventricular noncompaction cardiomyopathy：A case report","fulltext":[{"header":"Background","content":"\u003cp\u003eClozapine is an antipsychotic which always used in treatment-resistant schizophrenia and can reduce suicide rate for the patients [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. It is associated with severe cardiac complications including myocarditis and cardiomyopathy in psychotic patients[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Left ventricular noncompaction cardiomyopathy (LVNC) has been reported in patient with chronic clozapine use [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, the safety data of clozapine use during pregnancy and lactation are very limited. Clozapine can cross the placental barrier, decreased fetal heart rate variability and absence of accelerations have been found in previous cases[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Neonatal cardiomyopathy induced by clozapine has not been reported before. The case we report may increase the safety data of clozapine during pregnancy and lactation.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA premature neonate at 35 + 5 weeks gestation was delivered by caesarean section due to abnormal fetal fetal heart rate (FHR) in local hospital. Her mother had been taking clozapine 250mg during pregnancy because of schizophrenia. FHR monitoring has been suggestive slow since 30 weeks gestation. Abnormal myocardial injury markers and neonatal pneumonia was found after she was born. Her symptom improved after 9 days of treatment with sodium creatine phosphate, high doses of vitamin C and SULPERAZON. However, 25 days later, she developed poor response and milk consumption decreased by 1/3. Then she was admitted to our hospital. We learned that after she was discharged from the hospital, her mother was still taking clozapine and breast-feeding her. We told the mother to stop breastfeeding. On the second day, Myocardial injury markers were significantly increased with NT-probNP 14011.7pg/ mL. CTnI 14.57ng/ml and CK-MB 71.29ng/ml. Echocardiography showed the right ventricle (RV) increased to 5.9mm in anteroposterior diameter. The density of muscle wall, septum and outflow tract of RV increased widely. Right ventricular systolic and diastolic function reduced, but left ventricular systolic function was in the normal range. At that time, extensive myocardial calcification was considered. Electrolyte test showed serum calcium, magnesium, phosphorus was 2.15mmol/L, 0.84mmol/L, 3.35mmol/L respectively. Parathyroid hormone and vitamin D were normal. No calcium deposits in other organs were found by ultrasound in liver, gallbladder, spleen and brain. Tandem mass spectrometry was examined at an out-of-hospital facility, showed genetic metabolites no abnormalities. We considered that the small possibility of myocardial calcification caused by abnormal calcium, phosphorus metabolism and genetic metabolism. Creatine phosphate sodium, spironolactone, hydrochlorothiazide, and supportive therapy inciuding non-invasive ventilator, oxygen inhalation, warmth, sputum aspiration, nutrition were given, but no improvement, her right atria (RA) and RV were progressively dilated in a few short days, On day 5, the myocardium of the RV was thickened, especially free wall. Sinusoidal changes were seen at the apex of the RV, and the motion of the wall was obviously weakened. Captopril, milrinone and dobutamine were subsequently added, but can't reverse the conditions. Aditionally, we pursued evidence of viral infection, all the antibodies of EB virus, coxsackie virus, rubella virus, cytomegalovirus, herpes simplex virus and toxoplasma were negative. Antinuclear antibody line analysis showed no abnormalities too. The whole exome sequencing(WES) of the child and her parents did not find pathogenic or suspected pathogenic variants that clearly explained the her phenotype. However, Some variants defined as \"variant of uncertain significance(VUS)\" in the American College of Medical Genetics(ACMG) rating were detected, including AGXT, ARHGAP31,EYA4, FLT4, NCACNA1D, KMT2D and SCN5A (Table\u0026nbsp;1).\u003c/p\u003e\u003cp\u003eOn the 13th day of admission, the anteroposterior diameter of RV dilated to 14mm, while the RA dilated to 23*18mm. Non-compact layer: compact layer \u0026gt; 2. The echo of interventricular septum was uneven and strip-shaped. Echocardiography study showed prominent trabecular meshwork with deep intert rabecular recesses in the RV apex. Color flow Doppler examination confirmed the presence of blood flow within the trabeculae. Neither apical segment nor RV wall had obvious pulse, ventricular septal pulse stiff. It was seen that change rate of RV area was less than 10%. The LV become a D shape oppressed by augmented right heart. RVNC was diagnosed. Percutaneous oxygen saturation can only be maintained at 80–85% even with invasive respiratory support (FiO2 100%), and accompanied by shortness of breath, obvious dyspnea, increased heart rate (160–170 beats/min), poor response. The family eventually abandoned all treatment.\u003c/p\u003e"},{"header":"Discussion and conclusions","content":"\u003cp\u003eAccording to national databases reporting adverse drug effects, the rate of cardiomyopathy in clozapine treated patients in the U.S. was 8.9 per 100,000 person-years[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The Australian population has a higher incidence, Youssef DL et al[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]evaluated 129 Australia patients initiated on clozapine, analysed the incidence of clozapine-induced myocarditis and cardiomyopathy was 3.88% and 4.65% respectively. A systematic review of the literature on cardiomyopathy associated with clozapine concluded that symptoms developed at an average of 14.4 months after initiating clozapine. The clinical presentation was generally consistent with heart failure, including shortness of breath (60%) and palpitations (36%). Echocardiography showed dilated cardiomyopathy in 39% of cases and was not specified in other cases[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. In the reported cases of clozapine induced cardiotoxicity, the most common manifestations were reduced LVEF, left heart dilation and LVNC[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. However, our case presented with RVNC and right heart failure absence of reduction in LVEF and other coexisting cardiac abnormalities (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eVentricular noncompaction typically displays a dense trabecular meshwork with deep intertrabecular recesses, with the most commonly involved site being the LV and the RV only in a paucity of cases[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The pathogenesis of ventricular noncompaction is still unclear. Recent studies have revealed that gene mutation is an important etiology[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. However, all the variants for the child were accessed as AUS by ACMG rating. The genetic mode of the variants were autosomal dominant(AD) except for AGXT, but AGXT-related disease is primary hyperoxaluria type 1, which does not match the phenotype of the child. Furthermore, the parents denied genetic and metabolic disease and had no associated clinical manifestations. Therefore, We considered that none of these might be pathogenic genes.\u003c/p\u003e\u003cp\u003eClozapine can cross the placental barrier as well as breast milk[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], there have been cases of foetuses exposed to clozapine who have demonstrated decreased heart rate variability[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Sedation and adverse hematologic effects have been reported during lactation[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. However, neonatal cardiomyopathy exposed to clozapine during pregnancy and lactation has not been reported. Schoretsanitis G et al[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] reviewed the concentrations of antipsychotics in maternal blood (serum or plasma), amniotic fluid, umbilical cord blood, and/or breast milk. The penetration ratios of clozapine for amniotic fluid, umbilical cord blood, and breast milk to maternal blood ranged 0.31–0.82, 0.39–0.58, 2.79–4.32 respectively. Noteworthily, the concentration of clozapine in breast milk was several times that of the maternal blood.\u003c/p\u003e\u003cp\u003eIn our case, the mother took clozapine until 29 days after the baby birth. FHR(fetal heart rate) monitoring consistently suggested slow since 30 weeks gestation in utero. At birth, myocardial injury markers was significantly increased, then the infant were breastfed for more than 20 days. There was no obvious intrauterine infection observed, and no abnormality found in the screening of immune and metabolic diseases. Therefore, we considered that passive exposure to clozapine during both pregnancy and lactation may have contributed to the outcome of the infant.\u003c/p\u003e\u003cp\u003eIn conclusion, taking clozapine during pregnancy or lactation may cause cardiomyopathy for fetus and neonate. Although the mechanism is unclear for the neonatal ventricular noncompaction caused by clozapine, it reminds us that fetal monitor may need to be more frequent and breastfeeding is better to avoid when clozapine must be taken.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specifc Grant from funding agencies in the public, commercial, or not-for-proft sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe would like to thanks the patient and her family for giving us permission to publish this case report.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eYang Wen and Han Wang are the researchers of the article, and Yang Wen 's contribution provides credit and assumes responsibility. Han Wang provided information search and contributed partially to the writing of the article.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eHennen J, Baldessarini RJ (2005) Suicidal risk during treatment with clozapine: a meta-analysis. Schizophr Res 73(2):139\u0026ndash;145 \u003c/li\u003e\n\u003cli\u003eAlawami M, Wasywich C, Cicovic A, Kenedi C. A systematic review of clozapine induced cardiomyopathy. Int J Cardiol. 2014 Sep 20;176(2):315-20. doi: 10.1016/j.ijcard.2014.07.103.\u003c/li\u003e\n\u003cli\u003eFinsterer J, St\u0026ouml;llberger C. Noncompaction and Dilated Cardiomyopathy in a Patient with Schizophrenia. Case Rep Cardiol. 2016;2016:7384264. doi: 10.1155/2016/7384264. Epub 2016 Jul 31.\u003c/li\u003e\n\u003cli\u003eGuyon L, Auffret M, Coussemacq M, B\u0026eacute;n\u0026eacute; J, Deruelle P, Gautier S (2015) Alteration of the fetal heart rate pattern induced by the use of clozapine during pregnancy. Therapie 70(3):301\u0026ndash;303 \u003c/li\u003e\n\u003cli\u003eYogev Y, Ben-Haroush A, Kaplan B (2002) Maternal clozapine treatment and decreased fetal heart rate variability. Int J Gynecol Obstet 79(3):259\u0026ndash;260.\u003c/li\u003e\n\u003cli\u003eNovikova N, Chitnis M, Linder V, Hofmeyr GJ. Atypical antipsychotic (clozapine) self-poisoning in late pregnancy presenting with absent fetal heart rate variability without acidosis and delayed peristalsis in the newborn baby: a case report. Aust N Z J Obstet Gynaecol. 2009 Aug;49(4):442-4. doi: 10.1111/j.1479-828X.2009.01017.x.\u003c/li\u003e\n\u003cli\u003eLa Grenade L, Graham D, Trontell A. Myocarditis and cardiomyopathy associated with clozapine use in the United States. N Engl J Med Jul 19 2001;345(3):224\u0026ndash;5. \u003c/li\u003e\n\u003cli\u003eYoussef DL, Narayanan P, Gill N. Incidence and risk factors for clozapine-induced myocarditis and cardiomyopathy at a regional mental health service in Australia. Australas Psychiatry. 2016 Apr;24(2):176-80. doi: 10.1177/1039856215604480.\u003c/li\u003e\n\u003cli\u003eBellissima BL, Tingle MD, Cicović A, Alawami M, Kenedi C. A systematic review of clozapine-induced myocarditis. Int J Cardiol. 2018 May 15;259:122-129. doi: 10.1016/j.ijcard.2017.12.102.\u003c/li\u003e\n\u003cli\u003eBekheit S, Karam B, Daneshvar F, Zaidan J, Tabet R, Spagnola J, Lafferty J. Sudden cardiac death in isolated right ventricular hypertrabeculation/noncompaction cardiomyopathy. Ann Noninvasive Electrocardiol. 2018 Jul;23(4):e12487. doi: 10.1111/anec.12487.\u003c/li\u003e\n\u003cli\u003evan Waning JI, Moesker J, Heijsman D, Boersma E, Majoor-Krakauer D. Systematic Review of Genotype-Phenotype Correlations in Noncompaction Cardiomyopathy. J Am Heart Assoc. 2019 Dec 3;8(23):e012993. doi: 10.1161/JAHA.119.012993. \u003c/li\u003e\n\u003cli\u003eSchoretsanitis G, Westin AA, Deligiannidis KM, Spigset O, Paulzen M. Excretion of Antipsychotics Into the Amniotic Fluid, Umbilical Cord Blood, and Breast Milk: A Systematic Critical Review and Combined Analysis. Ther Drug Monit. 2020 Apr;42(2):245-254. doi: 10.1097/FTD.0000000000000692.\u003c/li\u003e\n\u003cli\u003ehttps://www.e-lactancia.org/breastfeeding/clozapine/product/\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7735073/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7735073/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eClozapine is an atypical antipsychotic indicated for treatment-resistant schizophrenia.It is associated with severe cardiac adverse events including myocarditis and cardiomyopathy. We report a case of a neonate who developed right ventricular noncompaction cardiomyopathy (RVNC) after birth and eventually died of right heart failure. Her mother had been taking clozapine during pregnancy and lactation. We suspect clozapine is responsible for her cardiomyopathy.\u003c/p\u003e","manuscriptTitle":"Clozapine induced neonatal right ventricular noncompaction cardiomyopathy：A case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-26 13:27:02","doi":"10.21203/rs.3.rs-7735073/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8a3a1717-3461-4e0f-a827-defcb2096ea8","owner":[],"postedDate":"October 26th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-22T15:24:23+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-26 13:27:02","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7735073","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7735073","identity":"rs-7735073","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}