探討懷孕婦女服用抗精神病藥物對姙娠結果之影響
Investigation of Pregnancy Outcomes of Women Using Antipsychotic Drugs
中文摘要
研究背景：精神疾病在女性患者好發於育齡時期。根據最近研究報導顯示，孕婦服用抗精神病藥 物有可能造成不良姙娠結果，包括新生兒早產、低出生體重、出生體重小於或大於姙娠年齡、以 及增加孕婦剖腹產比率等。然而，懷孕婦女服用抗精神病藥物對姙娠結果之影響，特別是針對患 有精神分裂症者，國內至今缺乏大型資料庫研究，因此難以確切提供醫療專業人員和孕婦服用抗 精神病藥物之參考。
研究目的：本研究使用全國人口資料(nationwide population-based study)，探討懷孕婦女 服用抗精神病藥物，特別是患有精神分裂症孕婦，對於姙娠結果之影響。不良姙娠結果包括新生 兒低出生體重、早產、小於姙娠年齡、大於姙娠年齡與產婦剖腹產計五項。
研究方法：本研究以1996 年到 2003 年國家衛生研究院所提供之台灣全民健保研究資料庫 (Taiwan National Health Insurance Research Dataset, NHIRD)，門診處方及治療明細檔
（適用85～92 年資料）(CD 檔)、門診處方醫令明細檔(OO 檔)、住院檔(DD 檔)和承保資料 檔(ID 檔)，串連內政部「2001-2003 年的出生登記檔」；研究對象為患有精神分裂症(ICD-9-CM code 295, 排除 295.7- schizoaffective disorder)之單胞胎產婦。統計方法使用 Statistics Analysis System (SAS)統計軟體，在校正產婦個人、產婦配偶和新生兒特質等潛在干擾因子 後，利用多變項羅吉斯迴歸 (multiple logistic regression analysis)分析懷孕婦女服用抗精 神病藥物對姙娠結果之影響，結果以勝算比(adjusted odds ratio)、95%信賴區間
(confidence interval)和 p-value <0.05 作為統計上顯著差異。
研究結果：本研究對象為收錄於全民健保資料庫中，患有精神分裂症(ICD-9-CM code 295) 696 名單胞胎產婦，以及隨機選取同期間資料庫中 3,480 位無精神分裂症之一般懷孕婦女。結 果發現，接受典型抗精神病藥物治療產婦，相較於姙娠期間未接受抗精神病藥物治療產婦，其新 生兒早產勝算比高達2.48 (crude OR=2.48, p<0.001)；但是，不論校正前後，產婦於姙娠 期間接受非典型抗精神病藥物治療之不良姙娠結果勝算比，相較於產婦姙娠期間未接受抗精神病 藥物治療，在統計上並無顯著差異。另外，無精神分裂症之正常懷孕婦女，新生兒低出生體重之 勝算比和小於姙娠年齡之勝算比，皆較精神分裂症懷孕婦女偏低，且呈現統計上顯著差異。
結論：本研究為迄今第一篇以全民健保資料庫，探討2001 年至 2003 年期間，懷孕婦女服用 抗精神病藥物對姙娠結果之影響。本研究發現，相較於姙娠期間未接受抗精神病藥物治療產婦，
精神分裂症孕婦接受接受非典型抗精神病藥物治療，其不良姙娠結果並無統計上差異，但是精神 分裂症孕婦服用典型抗精神病藥物，其新生兒早產危險性，在統計上呈現倍數增加。本研究的發 現期盼有助於提供醫療專業人員和孕婦服用抗精神病藥物之諮詢參考。
英文摘要
Background: The age of onset of psychotic disorders is usually before or during the
childbearing years. Several studies reported that women using antipsychotics may increase adverse pregnancy outcomes, particularly infant low birthweight (LBW), preterm birth, small for gestational age (SGA), large for gestational age (LGA) and maternal cesarean delivery during the past few years. However, the safety of antipsychotics on pregnancy outcome, especially for women with schizophrenia in Taiwan, remains unclear.
Objectives: The purpose of this nationwide population-based study was to compare the risk of adverse pregnancy outcomes between mothers with schizophrenia receiving antipsychotics during pregnancy and comparison subjects. The adverse pregnancy outcomes including preterm birth, LBW, LGA, SGA and maternal cesarean delivery.
Methods: This study linked two nationwide population-based datasets. The first dataset was obtained from the Taiwan National Health Insurance Research Dataset (NHIRD) and the second from the 2001-2003 birth certificate registry published by the Ministry of Interior. The Statistics Analysis System (SAS) statistical package was used to perform the analyses in this study. Multivariate logistic regression analysis was performed to explore the risk of adverse pregnancy outcomes between
schizophrenia mothers and nonschizophrenia mothers after adjusting for the characteristics of mother, father and infant. The odds ratios (OR) and 95%
confidence intervals (CI) for the estimated ORs were calculated. A two-sided p-value of <0.05 was considered statistically significant for this study.
Results: A total of 696 mothers with schizophrenia and singleton live births between January 1, 2001 and December 31, 2003 were included as the study group and 3,480 randomly selected pregnant women as a comparison group. As compared with maternal schizophrenia who did not receive antipsychotics during pregnancy, schizophrenia mothers who received typical antipsychotics during pregnancy had higher odds of preterm births (OR=2.48, 95% CI=1.51-4.08, p<0.001).
Nevertheless, schizophrenia mothers who received atypical antipsychotics during pregnancy did not have higher odds of LBW infants, preterm births, SGA or LGA babies. And mothers with schizophrenia, whether receiving antipsychotics or not during pregnancy, had increased risks for delivering babies with LBW and SGA than the comparison cohort.
Conclusions: To the best of our knowledge, this is the first nationwide
population-based study to investigate the risk of adverse pregnancy outcomes among mothers with schizophrenia receiving typical, atypical, and no antipsychotics during pregnancy and comparison subjects from the NHIRD database in Taiwan.
This study indicate that comparing to mothers with schizophrenia who received no antipsychotics during pregnancy, there were no higher risks of adverse pregnancy outcomes observed among those receiving atypical agents. The findings of the current study may help clinicians understand the possible impact of antipsychotics on pregnancy outcome and indicate a better clinical option for optimal control of schizophrenic symptoms during pregnancy.
