Factors Influencing Apnea and Bradycardia of Prematurity – Implications for Neurodevelopment

Abstract

Background: Apnea and bradycardia of prematurity (ABP) are possible risks towards damage of the developing brain. Objectives: To characterize the influence of neonatal factors on ABP and to determine the relationship of ABP to neurodevelopmental outcome. Methods: ABP was described in very low birth weight infants (n = 83) using the frequency and severity of ABP episodes with a clinical score considering heart rate, oxygenation, duration and interventions performed during each episode. Neonatal factors were analyzed for their relationship to ABP using regression analysis. Neurodevelopment was investigated using the Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) of the Bayley Scales of Infant Development II at a corrected age of 13 months. Power of ABP parameters to predict outcome was assessed by logistic regression analysis. Results: ABP typically started within the first week after birth. Spontaneous resolution occurred at a postmenstrual age (PMA) of 36.0 ± 2.2 (31.1–44.1) weeks. A delayed resolution (>36 weeks PMA) and a higher average daily ABP score during a defined developmental period (31–37 weeks PMA) were associated with a higher incidence of unfavorable outcome (MDI or PDI <69 or death). Conclusion: ABP is an age-specific phenomenon. However, more severe courses than expected for PMA or the resolution at a later PMA indicated an increased risk of neurodevelopmental disturbances at a corrected age of 13 months.

Intermittent Hypoxic Episodes in Preterm Infants: Do They Matter?

“…Despite these limitations, available data suggest a link between the number of days of apnea plus the number of days of assisted ventilation, and impaired neurodevelopmental outcome [40] . A relationship has also been shown between delay in resolution of apnea and bradycardia beyond 36 weeks' corrected age and a higher incidence of unfavorable neurodevelopmental outcome [4] . Future studies might better focus on the incidence and severity of desaturation events, as the technical ability to do this is now available, and it is likely that recurrent hypoxia is the detrimental feature of the immature respiratory control exhibited by preterm infants.…”

“…Several studies have shown that excessive or persistent apnea and bradycardia are associated with longer-term neurodevelopmental problems [4] . However, a causal relationship is hard to document and the role of accompanying desaturation is unclear.…”

Real-time detection, classification, and quantification of apneic episodes using miniature surface motion sensors in rats

“…However, hypopneic and obstructive apneic episodes are usually suspected only when bradycardia and hypoxemia are present, and the infants are already in severe distress or faint (7,(12)(13)(14)17,29). Repeated occurrences of hypoxemic episodes have been associated with impaired neurodevelopment, including mental retardation, cerebral palsy, blindness, growth retardation, and severe learning difficulties (4,15,17,30,31). Thus, timely detection and characterization of hypopneic and apneic episodes is of utmost importance.…”

Comparison of Aminophylline Alone and in Combination with Doxapram For Cessation of Apnea of Prematuriy

“…Recurrent episodes of apnea has significant impact on the blood flow to the vital organs including cerebral ischemia leading to undesired long term poor neuro developmental outcomes such as spastic diplagia. 2,3,4 The prolonged episode of apnea may sometimes require vigorous resuscitation due to fall of blood pressure during the episode and may lead to respiratory failure and death. The evidence is increasing that neonatal apnea is not only associated with brain damage but it may indeed reflect early disturbance of respiratory control system which may predispose infants to SIDS 5. Therefore aggressive approach in prevention and its management which includes specific therapy for the predisposing factors (such as hypoxia, hypothermia, hypoglycemia, infection and gastroesophageal reflux), tactile stimulation and noninvasive respiratory therapy has become increasingly important to stimulate the respiration.…”

“…Methylxanthines, such as caffeine, and aminophylline are the mainstay pharmacological treatment for apnea and have proven to reduce chronic lung disease and long-term outcome. 6,7 Doxapram was also used to treat neonates with persistent idiopathic apnea of prematurity unresponsive to methyl xanthenes therapy 8, 9. It is a good respiratory stimulant and increases breathing by stimulating both central and peripheral chemoreceptors 10,11. A number of observational trials have proved the efficacy of the individual drug in the successful reduction of the recurrent apnea and their short term and long term side effects. Here we have compared the efficacy, safety & short term outcomes of aminophylline mono therapy and in combination with doxapram in unresponsive neonatal apnea.…”