Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Psychological & Brain Sciences, Indiana University-Bloomington.
JAMA Netw Open. 2021 Apr 1;4(4):e215245. doi: 10.1001/jamanetworkopen.2021.5245.
Atopic dermatitis is associated with substantial morbidity in childhood. Further understanding of the underlying factors contributing to its onset is needed.
To assess the association of exposure to antibiotics in the prenatal period and early childhood with risk of atopic dermatitis in a nationwide population in Sweden.
DESIGN, SETTING, AND PARTICIPANTS: This Swedish nationwide, register-based, prospective cohort study used data on mother-child pairs from the Swedish Medical Birth Register linked to other national registers for information on health, socioeconomic, and demographic data. Participants were followed up until an atopic dermatitis outcome, emigration, death, or the end of the study on December 31, 2015. Data for all singleton children and discordant siblings born between March 1, 2006, and December 31, 2010, were included. Data were analyzed from June 1, 2020, to October 31, 2020.
Maternal exposure to systemic antibiotics during pregnancy as well as the child's exposure to systemic antibiotics during the first year of life, as defined by a dispensed prescription in the Swedish Prescribed Drug Register.
Time-to-event analyses were used to estimate the risk of outcome using attained age as a time scale. Atopic dermatitis was defined based on diagnoses in the National Patient Register and medication listed in the Swedish Prescribed Drug Register. Sibling-control analysis was performed to account for shared familial factors.
Among the 722 767 singleton children, the mean (SD) age was 5.8 (2.4) years and 351 589 (48.6%) were female. During the follow-up period, 153 407 children (21.2%) were exposed to antibiotics in utero and 172 405 children (23.8%) were exposed during the first year of life. The risk of atopic dermatitis among children exposed to prenatal antibiotics was greater than that among children who were not exposed (adjusted hazard ratio [aHR], 1.10; 95% CI, 1.09-1.12). In the sibling-control analysis, no association was observed (aHR, 0.96; 95% CI; 0.92-1.00). Exposure to antibiotics during the first year of life was associated with a greater risk of atopic dermatitis (aHR, 1.52; 95% CI, 1.50-1.55), with attenuated associations in the sibling-control analysis (aHR, 1.24; 95% CI, 1.20-1.29).
In this cohort study, exposure to antibiotics in early life was associated with an increased risk of atopic dermatitis in the general Swedish population, but this risk was partially confounded by familial factors. Research on the ways in which antibiotic use and other shared familial factors affect other atopic diseases may be warranted.
特应性皮炎与儿童时期的大量发病有关。需要进一步了解导致其发病的潜在因素。
评估瑞典全国人群中产前和幼儿期接触抗生素与特应性皮炎风险之间的关联。
设计、地点和参与者:本研究是一项瑞典全国范围内、基于登记的前瞻性队列研究,使用了来自瑞典医疗出生登记处的母婴对子数据,并与其他国家登记处的健康、社会经济和人口统计数据相关联。参与者的随访时间直至出现特应性皮炎结局、移民、死亡或 2015 年 12 月 31 日研究结束。包括 2006 年 3 月 1 日至 2010 年 12 月 31 日之间出生的所有单胎儿童和不一致的兄弟姐妹的数据。数据于 2020 年 6 月 1 日至 2020 年 10 月 31 日进行分析。
妊娠期间母亲接触全身性抗生素,以及瑞典处方药物登记处规定的儿童在生命的第一年接触全身性抗生素,作为处方药物。
使用获得的年龄作为时间尺度的时间事件分析来估计结局的风险。特应性皮炎是根据国家患者登记处的诊断和瑞典处方药物登记处列出的药物来定义的。进行了兄弟姐妹对照分析,以考虑到共同的家族因素。
在 722767 名单胎儿童中,平均(SD)年龄为 5.8(2.4)岁,351589 名(48.6%)为女性。在随访期间,153407 名儿童(21.2%)在子宫内接触过抗生素,172405 名儿童(23.8%)在生命的第一年接触过抗生素。与未接触过抗生素的儿童相比,接触过产前抗生素的儿童患特应性皮炎的风险更高(调整后的危险比[aHR],1.10;95%CI,1.09-1.12)。在兄弟姐妹对照分析中,未观察到相关性(aHR,0.96;95%CI,0.92-1.00)。生命第一年接触抗生素与特应性皮炎风险增加相关(aHR,1.52;95%CI,1.50-1.55),在兄弟姐妹对照分析中相关性减弱(aHR,1.24;95%CI,1.20-1.29)。
在这项队列研究中,在生命早期接触抗生素与瑞典普通人群中特应性皮炎的风险增加有关,但这种风险部分受到家族因素的混杂。可能有必要研究抗生素使用和其他共同的家族因素如何影响其他特应性疾病。