Caffeine Treatment for Premature Baby Apnea: Benefits Outweigh Harms

more than 30 years ago, clinicians found that methylxanthines reduced the incidence of prematureapnea in infantsSince then, methyl jaundice has become part of routine clinical treatment for preterm infants with apnea, and because the caffeine in this drug has a longer half-life in theinfant, it is most commonly used in clinical treatmentHowever, caffeine can reduce brain blood flow in adults (caffeine may be slightly higher for adults than the recommended dose forinfanttherapy), and inhibits adenosine receptors, which may counteract the protective effect of caffeine on brain cells in the absence of oxygenThese potential adversemay cause damage to the central nervous system and have adverse effects on long-term neurodevelopmentCaffeine also has a known effect - increasing metabolic and oxygen consumption, which may also have adverse effects on the long-term growth of infantsAlthough experts have been concerned about the potential long-term risks of caffeine, there is a lack of research evidence in this regardCaffeine treatment effects were evident
due to the above-mentioned uncertainties in the benefits and risks of caffeine treatment, the researchers designed a multicenter, randomized, placebo-controlled clinical study to evaluate the effectiveness of caffeine treatment for preterm infants with a birth weight of 500 to 1250 gPrior to this, a study published in the New England Journal of Medicine found a significant decrease in the incidence of bronchopulmonary dysplasia (BPD) in premature babies randomly assigned to caffeine treatmentThe only adverse result observed was that infants in the caffeine treatment group gained less weight in the first 3 weeks of treatment than in the placebo group However, it is not clear whether the reduction in the incidence of bronchial dysplasia translates into improvements in long-term neurodevelopmental outcomes, or whether the reduction in weight gain is a precursor to future growth In the November 8, 2007 issue of the New England Journal of Medicine, Schmidt et al reported on the long-term follow-up results of the study, which found that infants randomly assigned to caffeine treatment had improved survival rates at a correction age of 18 to 21 months, and were not accompanied by neurological abnormalities, which was the main observational outcome of the study Moreover, the incidence of cerebral palsy and cognitive lag decreased in the caffeine group compared to infants in the placebo treatment group, and there was no significant difference in the incidence of death, deafness, and blindness between the two groups In addition, caffeine therapy had no effect on the infant's growth (based on height, weight, and head circumference) compared to placebo therapy An analysis of the results (post hoc analysis) found that although there was no significant difference between the overall incidence of retinopathy in premature infants in the caffeine treatment group and the placebo group, the incidence of retinopathy in severe premature infants decreased Overall, the researchers estimate that treating 16 infants with caffeine could prevent one death or one surviving baby from having cerebral palsy, cognitive lag, blindness or deafness Efficacy also requires long-term follow-up
Why does methyl jaundice alkaloids improve the outcome of preterm infants with apnea? The mechanism of action of methyl jaundice alkaloids is complex, mainly by stimulating the respiratory center, but also to block adenosine receptors, and improve the function of the respiratory muscle Giving methyl jaundice alkaloids (e.g caffeine) increases the sensitivity of carbon dioxide and may also lower the threshold for carbon dioxide, which stimulates breathing when the arterial blood carbon dioxide fraction pressure (PaCO2) is low, and the ventilation level can be increased under a certain amount of PaCO2 In addition, caffeine can increase the amount of ventilation per cent Therefore, an analysis of previously published findings found that caffeine 55 percent of its effects were due to its reduced risk of respiratory support, oxygen supplementation, postpartum hormone therapy, and arterial catheterization (Patentductus arteriosus), and because caffeine reduced the incidence of bronchopulmonary dysplince All these effects ultimately lead to improved respiratory function in children But half of the effects of caffeine are inexplicable Other effects of caffeine therapy can also have beneficial effects in treating preterm babies with apnea, such as increasing catecholamine levels, which increase heart output and oxygenation However, there is no data on the effects of caffeine on the incidence and severity of hypoventilation and cardiac palpitations associated with apnea, and the mechanisms of effect on both may explain why caffeine improves long-term neurodevelopmental outcomes In addition to differences in liver function and renal function in the development of the infant, liver enzymes involved in caffeine biotransformation may also have genetic variations, which may lead to different reactions to caffeine therapy between individuals Some infants whose apnea persists after treatment for caffeine, indicating that the causes of preterm infants' apnea are varied, and other possible causes of apnea, such as respiratory obstruction, disease in the lungs due to instruosis Taken together with data from a previously published study, the data from Schmidt and others showed that while caffeine treatment for preterm infants' apnea leads to reduced weight gain in the first 3 weeks, it improves infant survival rates by 18 to 21 months of age, without neurodevelopmental abnormalities, and that the long-term effects of caffeine outweigh the benefits and disadvantages of their temporary adverse reactions Nevertheless, attention should be paid to long-term follow-up of caffeine-treated infants, as neurodevelopmental conditions at 18 to 21 months of age do not fully predict future neurodevelopmental outcomes and how these babies will perform in school in the future This newly published study provides support for treatments that have long been routine in clinical practice In this case, the doctor's experience is correct (or fortunate) to judge that the benefits of caffeine outweigh its risks before clinical studies have been proven But we're not always so lucky that for many treatments, it's often not tested by randomized, controlled trials, such as prenatal phenobarbital, which has shown that it doesn't prevent intra-brain bleeding, and that, for example, postpartum hormone therapy does naresonization of the bronchial lungs But for the treatment of caffeine for preterm infants with apnea, we can now conclude that the benefits of treatment outweigh the risks (Source N Engl J Med, 2007, 357:1968.) related link the long-term effects of caffeine treatment on preterm infants for apnea
background: methylxanthines are commonly used for the treatment of preterm infantaphem, but there is insufficient research data to demonstrate its efficacy and safety It is also unclear whether methyl jaundice alkaloids have long-term effects on neurodevelopment and the growth of children Methods: A total of 2006 premature babies with a birth weight of 500 to 1250g with apnea were randomly assigned to be treated with caffeine or placebo until treatment for apnea was no longer needed The main observation outcomes were the occurrence of death, cerebral palsy, cognitive lag (defined as a composite endpoint of 85 points for intelligent development index scores using the Bayley baby early childhood development scale) at a correction age of 18 to 21 months results: 3 out of 937 randomly assigned to caffeine treatment 77 (40.2%) cases of death or survival but neurodevelopmental abnormalities, while in 932 randomly assigned placebo-treated infants, 431 (46.2%) died or survived but had abnormal neurodevelopmental disorders (adjusted OR was 0.77, 95% CI was 0.64 to 0.93; P-0.008) Caffeine therapy compared to placebo treatment, cerebral palsy (4.4% vs 7.3%; adjusted OR 0.58; 95% CI for 0.39 to 0.87; P-0.009) and cognitive lag (33.8% vs 38.3%; adjustment OR 0.81; 95% CI 0.66 to 0.99; P.0.04) decreased The incidence of death, deafness and blindness, as well as the average percentage increase in height, weight and head circumference during follow-up, did not differ significantly between the two groups Conclusion: Caffeine treatment of preterm babies with very low birth weight can improve the survival rate at 18 to 21 months, and not associated with neurodevelopmental abnormalities (Source N Engl J Med, 2007, 357:1893-1902