分娩期间硬膜外镇痛与子代孤独症谱系障碍风险小幅增加相关
2021-10-04   阅读:423   来源:美国医学会杂志

加拿大英属哥伦比亚大学Tim F. Oberlander团队研究了分娩期间硬膜外镇痛与子代自闭症谱系障碍的相关性。相关论文于2021年9月28日发表在《美国医学会杂志》上。

研究表明,分娩过程中使用硬膜外镇痛与后代患自闭症谱系障碍(ASD)的风险之间存在相互矛盾的关系。

为了利用大量基于人群的数据集和ASD病例状态的临床数据,以评估产妇在分娩期间使用硬膜外镇痛与后代ASD的相关性,研究组进行了一项基于人群的回顾性队列研究,招募2000年4月1日至2014年12月31日在加拿大不列颠哥伦比亚省出生的足月单胎子女。不包括死产和剖宫产。临床ASD诊断数据来自不列颠哥伦比亚省自闭症评估网络和不列颠哥伦比亚省教育部。对所有儿童进行随访,直到临床诊断为ASD、死亡或研究结束日期2016年12月31日。

由儿科医生、精神病学家和接受过ASD评估专业培训的心理学家进行ASD临床诊断。Cox比例风险模型用于估计硬膜外镇痛和ASD的风险比。模型根据母亲的社会人口统计学、孕期母体状况、分娩和产前护理特征、婴儿性别、胎龄和胎龄大小状态进行了校正。

388254名儿童中49.8%为女童,平均胎龄为39.2周,平均随访9.05年后,共5192名儿童被诊断为ASD(1.34%)。111480名儿童暴露于母亲分娩时硬膜外镇痛(28.7%),94157名为女童,其中1710名(1.53%)被诊断为自闭症,276774分娩未经硬膜外镇痛的儿童(192510名为女童)中有3482名(1.26%)。未校正的危险比为1.32,完全校正的危险比为1.09。在女性内匹配条件logistic回归分析中,分娩时使用硬膜外镇痛与ASD之间没有统计学意义的关联,完全校正后的风险比为1.07。

研究结果表明,在这项以人群为基础的研究中,在分娩过程中使用硬膜外镇痛与达到统计学显著性阈值的后代患自闭症谱系障碍的风险小幅增加相关。然而,考虑到残留混淆可能导致的结果,这些发现并没有为这种关联提供强有力的支持证据。

附:英文原文

Title: Association of Epidural Analgesia During Labor and Delivery With Autism Spectrum Disorder in Offspring

Author: Gillian E. Hanley, Celeste Bickford, Angie Ip, Nancy Lanphear, Bruce Lanphear, Whitney Weikum, Lonnie Zwaigenbaum, Tim F. Oberlander

Issue&Volume: 2021/09/28

Abstract:

Importance  Evidence from studies investigating the association of epidural analgesia use during labor and delivery with risk of autism spectrum disorder (ASD) in offspring is conflicting.

Objective  To assess the association of maternal use of epidural analgesia during labor and delivery with ASD in offspring using a large population-based data set with clinical data on ASD case status.

Design, Setting, and Participants  This population-based retrospective cohort study included term singleton children born in British Columbia, Canada, between April 1, 2000, and December 31, 2014. Stillbirths and cesarean deliveries were excluded. Clinical ASD diagnostic data were obtained from the British Columbia Autism Assessment Network and the British Columbia Ministry of Education. All children were followed up until clinical diagnosis of ASD, death, or the study end date of December 31, 2016.

Exposures  Use of epidural analgesia during labor and delivery.

Main Outcomes and Measures  A clinical diagnosis of ASD made by pediatricians, psychiatrists, and psychologists with specialty training to assess ASD. Cox proportional hazards models were used to estimate the hazard ratio of epidural analgesia use and ASD. Models were adjusted for maternal sociodemographics; maternal conditions during pregnancy; labor, delivery, and antenatal care characteristics; infant sex; gestational age; and status of small or large for gestational age. A conditional logistic regression model matching women with 2 births or more and discordance in ASD status of the offspring also was performed.

Results  Of the 388254 children included in the cohort (49.8% female; mean gestational age, 39.2 [SD, 1.2] weeks; mean follow-up, 9.05 [SD, 4.3] years), 5192 were diagnosed with ASD (1.34%) and 111480 (28.7%) were exposed to epidural analgesia. A diagnosis of ASD was made for 1710 children (1.53%) among the 111480 deliveries exposed to epidural analgesia (94157 women) vs a diagnosis of ASD in 3482 children (1.26%) among the 276774 deliveries not exposed to epidural analgesia (192510 women) (absolute risk difference, 0.28% [95% CI, 0.19%-0.36%]). The unadjusted hazard ratio was 1.32 (95% CI, 1.24-1.40) and the fully adjusted hazard ratio was 1.09 (95% CI, 1.00-1.15). There was no statistically significant association of epidural analgesia use during labor and delivery with ASD in the within-woman matched conditional logistic regression (839/1659 [50.6%] in the exposed group vs 1905/4587 [41.5%] in the unexposed group; fully adjusted hazard ratio, 1.07 [95% CI, 0.87-1.30]).

Conclusions and Relevance  In this population-based study, maternal epidural analgesia use during labor and delivery was associated with a small increase in the risk of autism spectrum disorder in offspring that met the threshold for statistical significance. However, given the likelihood of residual confounding that may account for the results, these findings do not provide strong supporting evidence for this association.

DOI: 10.1001/jama.2021.14986

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