RARE DISEASE
Infantile apnea
Infantile apnea
Infantile apnea
Synonyms: Apnea in full-term infants, Apnea of infancy
Synonyms: Apnea in full-term infants, Apnea of infancy
Synonyms: Apnea in full-term infants, Apnea of infancy
Drug discovery
0
drugs
With orphan designations
Overview
Infantile Apnea Overview
Infantile apnea involves breathing pauses >20 seconds, often with bradycardia or oxygen desaturation, commonly affecting premature infants due to immature respiratory control. It may arise from idiopathic causes, prematurity, bronchopulmonary dysplasia, or congenital anomalies. Diagnosis relies on clinical monitoring and polysomnography. Management includes home apnea monitors, respiratory stimulation, CPAP, and caffeine therapy. Untreated cases risk neurodevelopmental and cardiovascular sequelae [1][6][15].
Burden
Associated with neurodevelopmental delays, failure to thrive, and cardiovascular strain (e.g., pulmonary hypertension) [6][11].
Chronic oxygen desaturation increases long-term morbidity risks, necessitating multidisciplinary follow-up [3][13].
Families face psychological stress and logistical challenges with home monitoring [1][8].
Therapies
Home monitoring: Continuous apnea-bradycardia monitors with caregiver education on stimulation/resuscitation [1][8].
Pharmacotherapy: Methylxanthines (e.g., caffeine) to enhance respiratory drive [8][15].
CPAP/surgery: For obstructive cases or refractory apnea; adenotonsillectomy if anatomic obstruction exists [3][11].
Categories: rare respiratory diseases
Research Papers
86 drug discovery papers about Infantile apnea, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
86 drug discovery papers about Infantile apnea, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2025-10-30 | Caffeine-associated reduction in patent ductus arteriosus is mediated in part by adenosine receptor antagonism.
Persistent patency of the ductus arteriosus (PDA) is less frequent among infants treated with caffeine for apnea of prematurity. Caffeine acts to inhibit A1, A2, and A3 adenosine receptors (ARs). Adenosine is typically vasodilatory, and serum adenosine levels are elevated in preterm newborns, suggesting a potential mechanism for caffeine-associated reduction in PDA. We hypothesized that caffeine has an indirect vasoconstrictive effect on the ductus by antagonizing specific ARs. The expression of AR subtypes in the mouse ductus was analyzed by RT-PCR on days 15, 17, 19 (full term) of gestation, and postnatal day 1. Pressure myography was used to examine responses of the isolated ductus to adenosine, caffeine (citrate or base), or preincubation with either caffeine or adenosine. AR immuno-localization and adenosine-mediated cyclic AMP (cAMP) generation were evaluated in human ductus smooth muscle cells (SMCs). A1AR, A2AAR, A2BAR, and A3AR were present and developmentally regulated in the mouse ductus. Adenosine promoted ductus dilation under fetal and newborn O2 conditions. Caffeine had little or no effect on ductus tone with concentrations spanning the therapeutic range and failed to augment O2-induced or cyclooxygenase inhibitor-stimulated ductus constriction. However, pretreatment with caffeine or selective A1AR and A2AAR antagonists prevented adenosine-induced ductus dilation. Caffeine also blocked adenosine-stimulated cAMP release in human ductus SMCs. In conclusion, caffeine did not induce direct ductus constriction ex vivo. However, caffeine exposure prevented adenosine-induced ductus relaxation, suggesting the inhibition of an endogenous vasodilator as a mechanism for the reduction in PDA.NEW & NOTEWORTHY Caffeine is a respiratory stimulant and one of the most commonly prescribed drugs in the NICU. Primarily used to reduce apnea of prematurity, additional therapeutic benefits have been noted, including decreasing the incidence of patent ductus arteriosus. Using mouse and human ductus models, we have identified a mechanism by which caffeine can promote ductus constriction by inhibiting adenosine-mediated vasodilation.
2025-10-06 | A Rare Nasopharyngeal Hemangioma Presenting as Recurrent Cyanotic Apnea in a Neonate: A Case Report and Literature Review.
Background: Infantile hemangiomas (IHs) are the most common vascular tumors of infancy, but airway involvement is rare and potentially life-threatening. While subglottic and laryngeal regions are most frequently affected, nasopharyngeal hemangiomas are exceptionally uncommon, particularly in premature infants presenting with nonspecific symptoms such as apnea and cyanosis. Case Presentation: We describe a female infant born prematurely at 35 weeks via cesarean section, who developed recurrent apnea and cyanotic episodes shortly after discharge. Flexible bronchoscopy revealed a nasopharyngeal mass causing upper airway obstruction, and imaging raised suspicion of a hemangioma. The patient underwent surgical excision of the lesion and was started on a tapering course of prednisolone. Postoperative recovery was favorable, and oral propranolol was initiated to prevent recurrence. At follow-up, the patient demonstrated normal development without respiratory symptoms. Conclusion: Nasopharyngeal hemangiomas are rare and may present subtly in premature infants. Early bronchoscopy and imaging should be considered in cases of unexplained apnea or airway compromise. A multidisciplinary approach ensures timely diagnosis and effective treatment, minimizing long-term respiratory complications.
2025-02-08 | Congenital vitamin D deficiency: presenting with feeding difficulty in early infancy: a case report.
Vitamin D deficiency remains a significant public health concern, particularly among exclusively breastfed infants. Infants born to mothers with vitamin D deficiency, often influenced by cultural factors affecting diet, lifestyle, and clothing, are at increased risk of developing early and potentially fatal complications of hypocalcemic vitamin D deficiency. While seizures and tetany are well-recognized manifestations of hypocalcemia in infants, less common symptoms, such as feeding difficulties and recurrent apnea, are rarely documented. . We present the case of a 50-day-old Ethiopian full-term infant, born to a Muslim Ethiopian mother, who experienced feeding difficulties, frequent brief episodes of apnea, and cyanosis since birth. The underlying cause was identified as hypocalcemia-induced laryngospasm due to congenital vitamin D deficiency, which resulted from maternal vitamin D deficiency. The mother, who has worn a niqab since childhood, had minimal sun exposure, contributing to her low vitamin D levels. The infant was successfully treated with intravenous calcium gluconate, followed by oral calcium and vitamin D supplementation, leading to complete resolution of symptoms and normalization of biochemical parameters. Hypocalcemia-induced laryngospasm presenting with feeding difficulties and recurrent apneic episodes is a rare yet serious clinical condition. This report emphasizes the need to consider hypocalcemia as a potential cause of unexplained feeding difficulties or recurrent apnea in newborns and infants. Therefore, clinicians should remain vigilant and maintain a high index of suspicion to ensure timely diagnosis and treatment. It is essential to measure serum calcium and vitamin D levels in both the mother and infant, particularly for newborns of high-risk mothers, such as those who wear conservative religious clothing like a niqab. Furthermore, routine biochemical screening for vitamin D deficiency should be incorporated into antenatal care for all high-risk mothers, with appropriate supplementation to prevent potential complications in both mothers and their infants.
2024-10-25 | Uncovering Diaphragm Cramp in SIDS and Other Sudden Unexpected Deaths.
The diaphragm is the primary muscle of respiration. Here, we disclose a fascinating patient's perspective that led, by clinical reasoning alone, to a novel mechanism of spontaneous respiratory arrests termed diaphragm cramp-contracture (DCC). Although the 7-year-old boy survived its paroxysmal nocturnal "bearhug pain apnea" episodes, essentially by breathing out to breathe in, DCC could cause sudden unexpected deaths in children, especially infants. Diaphragm fatigue is central to the DCC hypothesis in SIDS. Most, if not all, SIDS risk factors contribute to it, such as male sex, young infancy, rebreathing, nicotine, overheating and viral infections. A workload surge by a roll to prone position or REM-sleep inactivation of airway dilator or respiratory accessory muscles can trigger pathological diaphragm excitation (e.g., spasms, flutter, cramp). Electromyography studies in preterm infants already show that diaphragm fatigue and sudden temporary failure by transient spasms induce apneas, hypopneas and forced expirations, all leading to hypoxemic episodes. By extension, prolonged spasm as a diaphragm cramp would induce sustained apnea with severe hypoxemia and cardiac arrest if not quickly aborted. This would cause a sudden, rapid, silent death consistent with SIDS. Moreover, a unique airway obstruction could develop where the hypercontracted diaphragm resists terminal inspiratory efforts by the accessory muscles. It would disappear postmortem. SIDS autopsy evidence consistent with DCC includes disrupted myofibers and contraction band necrosis as well as signs of agonal breathing from obstruction. Screening for diaphragm injury from hypoxemia, hyperthermia, viral myositis and excitation include serum CK-MM and skeletal troponin-I. Active excitation could be visualized on ultrasound or fluoroscopy and monitored by respiratory inductive plethysmography or electromyography.
2024-04-09 | A Case Report of KCNT1 Mutation Presenting as Isolated Apnea and Bradycardia Events (P7-1.006)
Not applicable. A 5-day old male with no known perinatal complications presented with subclinical seizures as well as independent episodes of apnea with bradycardia occurring both while awake and asleep. Evaluation noted focal electrographic seizures originating from the left frontotemporal lobe without electrographic correlate to apnea and bradycardia events. MRI noted to be normal. Genetic evaluation noted a heterozygous likely pathogenic variant in KCNT1 (c.800T>C p.Met267Thr) suggesting causation of early infantile epilepsy and autonomic dysfunction. Interestingly, seizures resolved with the initiation of Levetiracetam. Not applicable. Not applicable. Traditionally, the differential diagnosis for full term neonatal apneic events include an immature nervous system, cerebral hemorrhage, respiratory compromise, infection, or seizure. This case emphasizes consideration for KCNT1 as an alternative cause of recurrent apnea and bradycardia episodes in neonates. It also implicates Levetiracetam as a possible successful treatment in early diagnosis of likely pathogenic KCNT1 mutations. Disclosure: Ms. Chorny has nothing to disclose. Dr. Galan has nothing to disclose.
small molecules
2025-10-30 | Caffeine-associated reduction in patent ductus arteriosus is mediated in part by adenosine receptor antagonism.
Persistent patency of the ductus arteriosus (PDA) is less frequent among infants treated with caffeine for apnea of prematurity. Caffeine acts to inhibit A1, A2, and A3 adenosine receptors (ARs). Adenosine is typically vasodilatory, and serum adenosine levels are elevated in preterm newborns, suggesting a potential mechanism for caffeine-associated reduction in PDA. We hypothesized that caffeine has an indirect vasoconstrictive effect on the ductus by antagonizing specific ARs. The expression of AR subtypes in the mouse ductus was analyzed by RT-PCR on days 15, 17, 19 (full term) of gestation, and postnatal day 1. Pressure myography was used to examine responses of the isolated ductus to adenosine, caffeine (citrate or base), or preincubation with either caffeine or adenosine. AR immuno-localization and adenosine-mediated cyclic AMP (cAMP) generation were evaluated in human ductus smooth muscle cells (SMCs). A1AR, A2AAR, A2BAR, and A3AR were present and developmentally regulated in the mouse ductus. Adenosine promoted ductus dilation under fetal and newborn O2 conditions. Caffeine had little or no effect on ductus tone with concentrations spanning the therapeutic range and failed to augment O2-induced or cyclooxygenase inhibitor-stimulated ductus constriction. However, pretreatment with caffeine or selective A1AR and A2AAR antagonists prevented adenosine-induced ductus dilation. Caffeine also blocked adenosine-stimulated cAMP release in human ductus SMCs. In conclusion, caffeine did not induce direct ductus constriction ex vivo. However, caffeine exposure prevented adenosine-induced ductus relaxation, suggesting the inhibition of an endogenous vasodilator as a mechanism for the reduction in PDA.NEW & NOTEWORTHY Caffeine is a respiratory stimulant and one of the most commonly prescribed drugs in the NICU. Primarily used to reduce apnea of prematurity, additional therapeutic benefits have been noted, including decreasing the incidence of patent ductus arteriosus. Using mouse and human ductus models, we have identified a mechanism by which caffeine can promote ductus constriction by inhibiting adenosine-mediated vasodilation.
2025-10-06 | A Rare Nasopharyngeal Hemangioma Presenting as Recurrent Cyanotic Apnea in a Neonate: A Case Report and Literature Review.
Background: Infantile hemangiomas (IHs) are the most common vascular tumors of infancy, but airway involvement is rare and potentially life-threatening. While subglottic and laryngeal regions are most frequently affected, nasopharyngeal hemangiomas are exceptionally uncommon, particularly in premature infants presenting with nonspecific symptoms such as apnea and cyanosis. Case Presentation: We describe a female infant born prematurely at 35 weeks via cesarean section, who developed recurrent apnea and cyanotic episodes shortly after discharge. Flexible bronchoscopy revealed a nasopharyngeal mass causing upper airway obstruction, and imaging raised suspicion of a hemangioma. The patient underwent surgical excision of the lesion and was started on a tapering course of prednisolone. Postoperative recovery was favorable, and oral propranolol was initiated to prevent recurrence. At follow-up, the patient demonstrated normal development without respiratory symptoms. Conclusion: Nasopharyngeal hemangiomas are rare and may present subtly in premature infants. Early bronchoscopy and imaging should be considered in cases of unexplained apnea or airway compromise. A multidisciplinary approach ensures timely diagnosis and effective treatment, minimizing long-term respiratory complications.
2025-02-08 | Congenital vitamin D deficiency: presenting with feeding difficulty in early infancy: a case report.
Vitamin D deficiency remains a significant public health concern, particularly among exclusively breastfed infants. Infants born to mothers with vitamin D deficiency, often influenced by cultural factors affecting diet, lifestyle, and clothing, are at increased risk of developing early and potentially fatal complications of hypocalcemic vitamin D deficiency. While seizures and tetany are well-recognized manifestations of hypocalcemia in infants, less common symptoms, such as feeding difficulties and recurrent apnea, are rarely documented. . We present the case of a 50-day-old Ethiopian full-term infant, born to a Muslim Ethiopian mother, who experienced feeding difficulties, frequent brief episodes of apnea, and cyanosis since birth. The underlying cause was identified as hypocalcemia-induced laryngospasm due to congenital vitamin D deficiency, which resulted from maternal vitamin D deficiency. The mother, who has worn a niqab since childhood, had minimal sun exposure, contributing to her low vitamin D levels. The infant was successfully treated with intravenous calcium gluconate, followed by oral calcium and vitamin D supplementation, leading to complete resolution of symptoms and normalization of biochemical parameters. Hypocalcemia-induced laryngospasm presenting with feeding difficulties and recurrent apneic episodes is a rare yet serious clinical condition. This report emphasizes the need to consider hypocalcemia as a potential cause of unexplained feeding difficulties or recurrent apnea in newborns and infants. Therefore, clinicians should remain vigilant and maintain a high index of suspicion to ensure timely diagnosis and treatment. It is essential to measure serum calcium and vitamin D levels in both the mother and infant, particularly for newborns of high-risk mothers, such as those who wear conservative religious clothing like a niqab. Furthermore, routine biochemical screening for vitamin D deficiency should be incorporated into antenatal care for all high-risk mothers, with appropriate supplementation to prevent potential complications in both mothers and their infants.
2024-10-25 | Uncovering Diaphragm Cramp in SIDS and Other Sudden Unexpected Deaths.
The diaphragm is the primary muscle of respiration. Here, we disclose a fascinating patient's perspective that led, by clinical reasoning alone, to a novel mechanism of spontaneous respiratory arrests termed diaphragm cramp-contracture (DCC). Although the 7-year-old boy survived its paroxysmal nocturnal "bearhug pain apnea" episodes, essentially by breathing out to breathe in, DCC could cause sudden unexpected deaths in children, especially infants. Diaphragm fatigue is central to the DCC hypothesis in SIDS. Most, if not all, SIDS risk factors contribute to it, such as male sex, young infancy, rebreathing, nicotine, overheating and viral infections. A workload surge by a roll to prone position or REM-sleep inactivation of airway dilator or respiratory accessory muscles can trigger pathological diaphragm excitation (e.g., spasms, flutter, cramp). Electromyography studies in preterm infants already show that diaphragm fatigue and sudden temporary failure by transient spasms induce apneas, hypopneas and forced expirations, all leading to hypoxemic episodes. By extension, prolonged spasm as a diaphragm cramp would induce sustained apnea with severe hypoxemia and cardiac arrest if not quickly aborted. This would cause a sudden, rapid, silent death consistent with SIDS. Moreover, a unique airway obstruction could develop where the hypercontracted diaphragm resists terminal inspiratory efforts by the accessory muscles. It would disappear postmortem. SIDS autopsy evidence consistent with DCC includes disrupted myofibers and contraction band necrosis as well as signs of agonal breathing from obstruction. Screening for diaphragm injury from hypoxemia, hyperthermia, viral myositis and excitation include serum CK-MM and skeletal troponin-I. Active excitation could be visualized on ultrasound or fluoroscopy and monitored by respiratory inductive plethysmography or electromyography.
2024-04-09 | A Case Report of KCNT1 Mutation Presenting as Isolated Apnea and Bradycardia Events (P7-1.006)
Not applicable. A 5-day old male with no known perinatal complications presented with subclinical seizures as well as independent episodes of apnea with bradycardia occurring both while awake and asleep. Evaluation noted focal electrographic seizures originating from the left frontotemporal lobe without electrographic correlate to apnea and bradycardia events. MRI noted to be normal. Genetic evaluation noted a heterozygous likely pathogenic variant in KCNT1 (c.800T>C p.Met267Thr) suggesting causation of early infantile epilepsy and autonomic dysfunction. Interestingly, seizures resolved with the initiation of Levetiracetam. Not applicable. Not applicable. Traditionally, the differential diagnosis for full term neonatal apneic events include an immature nervous system, cerebral hemorrhage, respiratory compromise, infection, or seizure. This case emphasizes consideration for KCNT1 as an alternative cause of recurrent apnea and bradycardia episodes in neonates. It also implicates Levetiracetam as a possible successful treatment in early diagnosis of likely pathogenic KCNT1 mutations. Disclosure: Ms. Chorny has nothing to disclose. Dr. Galan has nothing to disclose.
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