Apnea of prematurity (AOP) is one of the common diseases in preterm infants. The main cause of AOP is immature development of the respiratory control center. If AOP is not treated timely and effectively, it will lead to respiratory failure, hypoxic brain injury, and even death in severe cases. Caffeine is the first choice for the treatment of AOP, but its effectiveness varies in preterm infants. With the deepening of AOP research, more and more genetic factors have been confirmed to play important roles in the pathogenesis and treatment of AOP; in particular, the influence of single nucleotide polymorphism on the efficacy of caffeine has become a research hotspot in recent years. This article reviews the gene polymorphisms that affect the efficacy of caffeine, in order to provide a reference for individualized caffeine therapy. Citation.
Apnea/genetics* ; Caffeine/therapeutic use* ; Humans ; Infant ; Infant, Newborn ; Infant, Newborn, Diseases ; Infant, Premature ; Infant, Premature, Diseases ; Polymorphism, Single Nucleotide

OBJECTIVES: To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment. METHODS: A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group. RESULTS: Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05). CONCLUSIONS This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.
Caffeine/therapeutic use* ; Citrates ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Respiration, Artificial ; Retrospective Studies

OBJECTIVE: To compare the efficacy of domestic and imported caffeine citrate in the treatment of apnea in preterm infants. METHODS: A total of 98 preterm infants with a gestational age of 28 - <34 weeks between April 2018 and December 2019 were enrolled. They were randomly administered with domestic (n=48) or imported caffeine citrate (n=50) within 6 hours after birth. The therapeutic effects, complications, adverse effects and clinical outcomes were compared between the two groups. RESULTS: There were no significant differences in the incidence of apnea within 7 days after birth, daily frequency of apnea, the time of apnea disappearance, the failure rate of intubation-surfactant-extubation strategy, the time of non-invasive assisted ventilation, the duration of oxygen therapy, the duration of caffeine citrate therapy, the length of hospital stay, blood gas analysis results, liver and kidney function testing results between the two groups (P>0.05). There were no significant differences in the incidence of complications and the mortality rate between the two groups (P>0.05). There was no significant difference in the incidence of adverse effects between the two groups (P>0.05). CONCLUSIONS The efficacy and safety of domestic caffeine citrate in the treatment of apnea are similar to those of imported caffeine citrate in preterm infants.
Apnea ; drug therapy ; Caffeine ; therapeutic use ; Citrates ; therapeutic use ; Double-Blind Method ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Premature, Diseases ; Prospective Studies

OBJECTIVE: To study the clinical effect and safety of different maintenance doses of caffeine citrate in the treatment of apnea in very low birth weight preterm infants. METHODS: A total of 78 very low birth weight preterm infants with primary apnea were enrolled who were admitted from January 2016 to January 2018. They were randomly divided into high-dose caffeine group with 38 children and low-dose caffeine group with 40 children. Both groups received a loading dose of 20 mg/kg caffeine citrate, and 24 hours later, the children in the high-dose caffeine group were given a maintenance dose of 10 mg/kg, and those in the low-dose caffeine group were given a maintenance dose of 5 mg/kg. The two groups were compared in terms of response rate and incidence rate of adverse events. RESULTS: The high-dose caffeine group had a significantly higher response rate than the low-dose caffeine group (71% vs 48%; P<0.05). Compared with the low-dose caffeine group, the high-dose caffeine group had significantly shorter duration of apnea and time of caffeine treatment (P<0.05). There were no significant differences between the two groups in length of hospital stay and incidence rates of tachycardia, feeding intolerance, bronchopulmonary dysplasia, necrotizing enterocolitis, and intracranial hemorrhage (P>0.05). There was no significant difference in the mortality rate between the two groups (P>0.05). CONCLUSIONS Higher maintenance dose of caffeine citrate has a better clinical effect than lower maintenance dose of caffeine citrate in the treatment of apnea in very low birth weight preterm infants, without increasing the incidence rates of adverse drug reactions and serious complications in preterm infants.
Apnea ; drug therapy ; Caffeine ; therapeutic use ; Child ; Citrates ; therapeutic use ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies

Bronchopulmonary dysplasia (BPD) is one of the few diseases affecting premature infants that have continued to evolve since its first description about half a century ago. The current form of BPD, a more benign and protracted respiratory failure in extremely preterm infants, is in contrast to the original presentation of severe respiratory failure with high mortality in larger premature infants. This new BPD is end result of complex interplay of various antenatal and postnatal factors causing lung injury and subsequent abnormal repair leading to altered alveolar and vascular development. The change in clinical and pathologic picture of BPD over time has resulted in new challenges in developing strategies for its prevention and management. While some of these strategies like Vitamin A supplementation, caffeine and volume targeted ventilation have stood the test of time, others like postnatal steroids are being reexamined with great interest in last few years. It is quite clear that BPD is unlikely to be eliminated unless some miraculous strategy cures prematurity. The future of BPD prevention will probably be a combination of antenatal and postnatal strategies acting on multiple pathways to minimize lung injury and abnormal repair as well as promote normal alveolar and vascular development.
Adrenal Cortex Hormones ; therapeutic use ; Animals ; Bronchopulmonary Dysplasia ; prevention & control ; Caffeine ; therapeutic use ; Humans ; Oxygen ; therapeutic use ; Pulmonary Surfactants ; therapeutic use ; Respiration, Artificial

OBJECTIVETo investigate the effect of caffeine citrate treatment on early pulmonary function in preterm infants with apnea.

METHODSForty preterm infants with apnea were randomly divided into aminophylline treatment group (20 infants) and caffeine citrate treatment group (20 infants). When the preterm infants experienced apnea after birth, they were given aminophylline or caffeine citrate in addition to assisted ventilation with continuous positive airway pressure (NCPAP). After drug discontinuation, pulmonary function was measured and compared between the two groups.

RESULTSAfter treatment, compared with the aminophylline treatment group, the caffeine citrate treatment group had significantly higher tidal volume, minute ventilation volume, ratio of time to peak tidal expiratory flow to total expiratory time, ratio of volume to peak tidal expiratory flow to total expiratory volume, peak expiratory flow, and breathing flow at 75%, 50%, and 25% of tidal volume (P<0.05). The caffeine citrate treatment group had a significantly shorter time of oxygen use and NCPAP support than the aminophylline treatment group (P<0.01). Compared with the aminophylline treatment group, the caffeine citrate treatment group had a significantly lower frequency of apnea attacks (P<0.01).

CONCLUSIONSIn the treatment of apnea in preterm infants, caffeine citrate can improve early pulmonary function and reduce the incidence of apnea.

Aminophylline ; therapeutic use ; Apnea ; drug therapy ; physiopathology ; Caffeine ; pharmacology ; therapeutic use ; Citrates ; pharmacology ; therapeutic use ; Continuous Positive Airway Pressure ; Female ; Humans ; Infant, Newborn ; Infant, Premature ; Lung ; drug effects ; physiopathology ; Male

OBJECTIVETo assess the biological effects of the six-herb mixture Anti-Insomia Formula (AIF) extract using caffeine-induced insomnia Drosophila model and short-sleep mutants.

METHODSCaffeineinduced insomnia wild-type Drosophila and short-sleep mutant flies minisleep (mns) and Hyperkinetic(Y) (Hk(Y)) were used to assess the hypnotic effects of the AIF in vivo. The night time activity, the amount of night time sleep and the number of sleep bouts were determined using Drosophila activity monitoring system. Sleep was defined as any period of uninterrupted behavioral immobility (0 count per minute) lasting > 5 min. Night time sleep was calculated by summing up the sleep time in the dark period. Number of sleep bouts was calculated by counting the number of sleep episodes in the dark period.

RESULTSAIF at the dosage of 50 mg/mL, effectively attenuated caffeine-induced wakefulness (P<0.01) in wild-type Canton-S flies as indicated by the reduction of the sleep bouts, night time activities and increase of the amount of night time sleep. AIF also significantly reduced sleeping time of short-sleep Hk(Y) mutant flies (P<0.01). However, AIF did not produce similar effect in mns mutants.

CONCLUSIONAIF might be able to rescue the abnormal condition caused by mutated modulatory subunit of the tetrameric potassium channel, but not rescuing the abnormal nerve firing caused by Shaker gene mutation. This study provides the scientific evidence to support the use of AIF in Chinese medicine for promoting sleep quality in insomnia.

Animals ; Caffeine ; Chromatography, High Pressure Liquid ; Disease Models, Animal ; Drosophila melanogaster ; drug effects ; physiology ; Hypnotics and Sedatives ; pharmacology ; therapeutic use ; Mutation ; genetics ; Potassium Channels ; genetics ; Sleep ; drug effects ; Sleep Initiation and Maintenance Disorders ; drug therapy ; Wakefulness ; drug effects

OBJECTIVETo study the efficacy of early caffeine treatment in preterm infants with respiratory distress syndrome (RDS).

METHODSA prospective controlled clinical trial was performed. A total of 59 preterm infants with RDS were enrolled and divided into a caffeine group (30 infants) and a control group (29 infants). Caffeine was administered in the caffeine group and control group at the same dosage at 12-24 hours after birth and before extubation respectively. The respirator parameters and the incidence rates of ventilator-associated pneumonia (VAP) and apnea were compared between the two groups.

RESULTSCompared with the control group, the caffeine group had significantly lower peak inspiratory pressure, peak fraction of inspired oxygen, and incidence rate of VAP (p<0.05), as well as significantly shorter intubation time, NCPAP time, and total duration of oxygen supply (p<0.05). In addition, the caffeine group had a significantly longer time to first onset of apnea after extubation (p<0.05) and significantly fewer times of onset of apnea 1-2 days after extubation (p<0.01), as compared with the control group.

CONCLUSIONSEarly caffeine treatment can reduce the need for assisted ventilation in preterm infants with RDS, help with early extubation and ventilator weaning, reduce the oxygen time in the late stage, reduce the incidence of VAP, and prevent the development of apnea after extubation.

Apnea ; etiology ; Caffeine ; therapeutic use ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Prospective Studies ; Respiratory Distress Syndrome, Newborn ; complications ; therapy ; Ventilators, Mechanical

OBJECTIVETo investigate the current status of studies on drug therapy for apnea of prematurity (AOP) in the past decade in China and abroad, and to describe the research trends in the field.

METHODSCNKI and MEDLINE were searched with the key words "apnea of prematurity" and "treatment" for articles published in the past decade (January 2006 to December 2015). The articles were screened and the key words were extracted to establish the co-occurrence matrix. Ucinet 6.2 was used to plot the knowledge map.

RESULTSA total of 26 Chinese key words and 20 English key words were included. Those in the center of the co-existent knowledge map of Chinses keywords were "preterm infants", "apnea", "primary apnea", "naloxone" and "aminophylline"; while "apnea", "preterm infants" and "caffeine" located in the central place of the co-existent knowledge map of English keywords.

CONCLUSIONSMethylxanthines are still the major drugs for AOP; however, aminophylline is mainly used in China, while caffeine is mainly used in foreign countries. Other drugs such as naltrexone are also used in the clinical treatment of AOP.

Aminophylline ; therapeutic use ; Apnea ; drug therapy ; Caffeine ; therapeutic use ; Humans ; Infant, Newborn ; Infant, Premature ; Infant, Premature, Diseases ; drug therapy

INTRODUCTIONDriver fatigue is one of the biggest health and safety concerns within the road transport sector. This study aimed to find out the prevalence of fatigue among taxi drivers in Singapore, to better understand the general working and health conditions of this group of people and to determine the risk factors associated with fatigued driving.

METHODSA total of 340 taxi drivers were randomly selected for participation in this self-administered questionnaire survey, with height and weight measurements. The response rate was 68.2%. The survey consisted of four main categories: personal particulars; social habits; work patterns and sleep profile; and Epworth Sleepiness Scale, which was used to estimate the level of daytime sleepiness and fatigue. Multiple logistic regression analysis was used to estimate the adjusted odd ratios and 95% confidence intervals associated with the risk factors related to fatigue among the taxi drivers.

RESULTSA high proportion of the taxi drivers were obese and had self-reported hypertension, diabetes mellitus and high cholesterol. Driver fatigue was associated with very poor/poor self-rating of the quality of sleep, having an additional part-time job, drinking three or more caffeinated drinks daily, and driving more than 10 hours a day.

CONCLUSIONWe hope that the findings of the present study will improve the awareness regarding the work and health conditions of taxi drivers, and contribute toward the effort to achieve a healthier workforce. A lower prevalence of fatigued driving will lead to lower risks of road traffic accidents, decreased economic loss, increased productivity, and safer roads for all.

Adult ; Aged ; Automobile Driving ; Body Height ; Body Weight ; Caffeine ; therapeutic use ; Fatigue ; diagnosis ; epidemiology ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Occupational Diseases ; diagnosis ; epidemiology ; Prevalence ; Risk Factors ; Safety ; Singapore ; Sleep ; Surveys and Questionnaires ; Work Schedule Tolerance