11月28日,《儿科学》杂志在线发表的一项研究显示,预防性使用对乙酰氨基酚的确会轻微增加婴儿接种后睡眠时间但并不显著,解热药可能通过抑制机体自然免疫应答而实际上发挥对抗睡眠、甚至降低免疫应答水平的作用。在下午接种疫苗后体温迅速升高的婴儿在接种后24 h内的睡眠时间,明显长于在上午接种的婴儿以及接种后体温未升高的婴儿(Pediatrics 2011 Nov. 28 [doi:10.1542/peds.2011-1712])。
美国加州大学的Linda Franck博士及其同事从一项产后睡眠障碍研究中采集了预防性使用对乙酰氨基酚以减少婴儿接种疫苗后睡眠障碍的相关信息。共涉及70名相关资料齐全的婴儿,来自2个随机分组:对照组的母亲接受标准护理;强化组的母亲在接种前30 min预防性使用对乙酰氨基酚,接种后每4 h使用1次对乙酰氨基酚,共使用5剂。虽然经过了随机分组,但入组婴儿80%在接种时或接种后被使用了对乙酰氨基酚,不过对照组的使用时间更多在出现发热或不适症状后。
所有入组婴儿均佩戴了脚踝活动变化记录仪,记录接种前后24 h的活动数据,由此推测睡眠运动情况。母亲也通过日记记录婴儿的睡眠情况,并在每天早上采用电子温度计记录婴儿的腋窝温度,连续记录72 h。母亲的平均年龄为27岁,其中31%为亚裔,26%为白人,23%为西班牙裔,11%为黑人,9%为混血或其他种族;90%的母亲读完了中学,29%读完了大学。婴儿的平均年龄为9周,平均出生体重为3.4 kg;80%在入组时已接种了所有推荐接种的疫苗。
结果显示,强化组婴儿接种后24 h的腋窝温度显著高于接种前(平均升高0.23℃)。但组间差异不显著。强化组婴儿的睡眠时间也显著长于对照组(平均增加69 min),不过增加的主要是活动睡眠,而安静睡眠时间仅略微增加。研究者发现,睡眠时间延长与腋窝温度升高之间存在明显关联,与接种时间也有显著相关性:下午1:30以后接种的婴儿睡眠时间更长,而部分较早接种的婴儿的睡眠时间反而少于接种前。
多变量回归分析显示,只有接种后腋窝温度升高和下午接种者2个因素可预测接种后24 h睡眠时间延长,在后者中占32.5%的比重。
研究者指出,对照组亦有多数婴儿使用了对乙酰氨基酚,这使得更难发现组间差异。入组婴儿中仅有14名未使用该药,他们接种后的睡眠时间增加相对更多。不过,鉴于对乙酰氨基酚并非显著预测因素,研究者认为体温增加才是睡眠时间延长的主要原因。
研究者总结认为:“体温升高被认为是免疫应答的标志之一,而且与T细胞活性增加、抗原识别和免疫应答增强所伴随的内源性致热源释放有关。因此,接种疫苗后睡眠时间延长和体温升高可能是抗体应答程度的指标。”如果上述结果能得到进一步证实,或许应建议在下午对婴儿接种疫苗,以帮助婴儿更好地睡眠。
本项研究获得了美国国立卫生研究院的支持。研究者均无相关利益冲突。(生物谷Bioon.com)
doi:10.1542/peds.2011-1712
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Infant Sleep After Immunization: Randomized Controlled Trial of Prophylactic Acetaminophen
Linda Franck, RN, PhD, Caryl L. Gay, PhD, Mary Lynch, RN, MS, MPH, CPNP, Kathryn A. Lee, RN, PhD
Objective: To determine the effects of acetaminophen and axillary temperature responses on infant sleep duration after immunization. Methods: We conducted a prospective, randomized controlled trial to compare the sleep of 70 infants monitored by using ankle actigraphy for 24 hours before and after their first immunization series at ∼2 months of age. Mothers of infants in the control group received standard care instructions from their infants' health care provider, and mothers of infants in the intervention group were provided with predosed acetaminophen and instructed to administer a dose 30 minutes before the scheduled immunization and every 4 hours thereafter, for a total of 5 doses. Infant age and birth weight and immunization factors, such as acetaminophen use and timing of administration, were evaluated for changes in infant sleep times after immunization. Results: Sleep duration in the first 24 hours after immunization was increased, particularly for infants who received their immunizations after 1:30 pm and for those who experienced elevated temperatures in response to the vaccines. Infants who received acetaminophen at or after immunization had smaller increases in sleep duration than did infants who did not. However, acetaminophen use was not a significant predictor of sleep duration when other factors were controlled. Conclusions: If further research confirms the relationship between time of day of vaccine administration, increased sleep duration after immunization, and antibody responses, then our findings suggest that afternoon immunizations should be recommended to facilitate increased sleep in the 24 hours after immunization, regardless of acetaminophen administration.