探討妊娠婦女於懷孕期間服用抗類風濕性關節炎藥物對懷孕結果之影響

Investigation of Pregnancy Outcomes of Women Using Antirheumatic Agents during Pregnancy

王筱萍(Shiao-Ping Wang)

指導教授 ： 林恆慶

臺北醫學大學/公共衛生暨營養學院/醫務管理學研究所/碩士(2011年)

https://doi.org/10.6831/TMU.2011.00131

摘要

目的：本研究主要目的在於探討相較於沒有類風濕性關節炎的女性，類風濕性關節炎婦女於妊娠期間使用相關抗風類風濕性藥物在造成低出生體重(<2500 g)、早產(妊娠< 37週)、SGA嬰兒(出生體重低於該妊娠年紀的10個百分位)之風險及不同藥物間是否有不同的結果。
方法：本研究為以群眾為基礎的回溯性世代研究，以台灣的全民健康保險研究資料庫（NHIRD）和出生登記資料（NBCR）的數據進行分析。

結果：
以2001-2003為研究範疇，患有類風濕性關節炎者（ICD -9碼714.0）計1,912人，其中579人使用至少一類的抗類風濕性關節炎藥物，這些藥物包括非類固醇消炎藥物(NSAIDs)，類固醇(Steroids)以及非生物性疾病修飾抗風濕藥物（DMARDs）如sulfasalazine，hydroxychloroquine，cyclosporine 或azathioprin，將其餘1,333人設為對照組，兩組依年齡配對後進行分析。在控制產婦人口社經特徵、疾病與配偶年齡差異和新生兒特徵後，發現妊娠期間使用一類以上抗類風濕性關節炎藥物者，較對照組在低出生體重、早產以及SGA上分別有2.12倍（校正勝算比1.97，95％信賴區間為1.11-3.50），3.26倍（校正勝算比3.22，95％信賴區間為1.91-5.40）以及2.13倍（校正勝算比2.00，95％信賴區間為1.30-3.09）的風險。妊娠期間單獨使用一類藥物者較對照組在低出生體重、早產以及SGA上分別有1.55倍（校正勝算比1.50，95％信賴區間為1.03-2.19），1.92倍（校正勝算比1.93，95％ 信賴區間為1.34-2.77）以及1.39倍(校正勝算比1.38，95％ 信賴區間為1.05-1.83）的風險。妊娠期間使用NSAIDs產出低出生體重，早產及SGA嬰兒較對照組分別具有1.57倍（校正勝算比1.51，95％信賴區間為1.02-2.23），1.88倍(校正勝算比1.89，95％信賴區間為1.29-2.76)及1.34倍(校正勝算比1.33，95％信賴區間為0.99-1.78)風險。Steroids較對照組在早產兒及SGA風險分別為2.40(校正勝算比2.49，95％信賴區間為1.08-5.77)及2.27倍（校正勝算比2.34，95％信賴區間為1.22-4.49）。合併類固醇及非類固醇消炎藥物使用較對照組產出低出生體重，早產及SGA嬰兒分別具有2.44倍（校正勝算比2.30，95％信賴區間為1.19-4.45），4.30倍(校正勝算比4.17，95％信賴區間為2.39-7.42)及1.99倍(校正勝算比1.88，95％信賴區間為1.11-3.18)風險。

結論：
基於本研究結果發現，RA患者於妊娠期間無服用任何一種抗類風濕性關節炎藥物，不良懷孕結果風險機率與一般孕產婦相似。使用NSAIDs或Steroids等藥物，風險機率增大，為有效控制病情同時併用NSAIDs和Steroids時，風險具加成性。根據研究結果顯示，妊娠期間需服用藥物控制病情的RA患者，在胎兒生長發育上應較一般孕產婦需接受更密切的監測與評估，建議有關醫療單位可以對RA患者在妊娠期間提供更詳細的照護計畫。

關鍵字

妊娠 ； 類風濕性關節炎 ； 抗類風濕性關節炎藥物

並列摘要

Purpose：The main purpose of this study is to assess the risk of drug-caused adverse pregnancy outcome, such as low birth weight (<2500 g), preterm delivery (gestation <37 weeks), SGA infants (birth weight below the 10 percentile of corresponding gestational age), compared with RA women without antirheumatic agents, and to assess whether the use of different drugs have different results.

Method：This was a retrospective cohort study in which data from the National Health Insurance Research Database (NHIRD) and National birth certification registry (NBCR) in Taiwan were analyzed.

Result：The study cohort comprised 1,192 pregnant women between 2001-2003, in whom rheumatic patients( ICD-9 Code 174.0 )，579 cases used at least one class of antirheumatic agents, including NSAIDs, Steroids or nonbiologic DMARDs( sulfasalazine , hydroxychloroquine , cyclosporine or azathioprin ). The remaining 1,333 cases were set to control group. Two groups were matched by age and selected for analysis.
The odds ratio of the group using more than one class of anti-rheumatoid arthritis drugs during pregnancy were 2.12 (adjusted odds ratio 1.97, 95% CI 1.11-3.50), 3.26 (adjusted odds ratio 3.22, 95% CI 1.91-5.10) and 2.13 (adjusted odds ratio 2.00, 95% CI 1.30-3.09) in the low birth weight, prematurity and SGA respectively, compared with the control group. The odds ratio of the group using one class of drugs were 1.55 (adjusted odds ratio 1.50, 95% CI 1.03-2.19), 1.92 (adjusted odds ratio 1.93, 95%CI 1.34-2.77) and 1.39 (adjusted odds ratio 1.38, 95% CI 1.05-1.83) in the low birth weight, prematurity and SGA respectively, compared with the control one. The odds ratio of the group using NSAIDs were 1.57 (adjusted odds ratio 1.51, 95% CI 1.02-2.23), 1.88 (adjusted odds ratio 1.89, 95% CI 1.29-2.76) and 1.34 (adjusted odds ratio 1.33, 95% CI 0.99-1.78) in the low birth weight, prematurity and SGA respectively, compared with the control one. The odds ratio of the group using steroids were 2.40 (adjusted odds ratio in 2.49, 95% CI 1.08-5.77) and 2.27(2.34, 95% CI 1.19-4.49)in the prematurity and SGA respectively, compared with the control one. The odds ratio of the group with combined using of steroids and nonsteroidal anti-inflammatory drug were 2.44 (adjusted odds ratio 2.30, 95% CI 1.19-4.45), 4.30(adjusted odds ratio 4.17, 95 % CI 2.39-7.42) and 1.99(adjusted odds ratio 1.88, 95% CI 1.11-3.18) in the low birth weight, prematurity and SGA respectively, compared with the control one.

Conclusion：
Based on the findings, RA patients whom using NSAIDs or Steroids during pregnancy increased the risk of adverse pregnancy outcomes. For controlling the disease activity, combined use of NSAIDs and Steroids is necessary, but the risk is additive. The results show that for patients who need taking drugs to control the disease state, the fetal growth should be under closer monitoring and more evaluation than without using drug pregnant women. The department of health can set up more detail care plan for RA patients during pregnancy.

並列關鍵字

pregnancy ； rheumatic arthritits ； antirheumatic agent

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