懷孕中使用SSRI與新生兒肺高壓有關


  【24drs.com】根據一篇新研究,孕婦服用選擇性血清素再吸收抑制劑(SSRIs),可能會使她們的胎兒發生持續肺高壓的風險增加,那是種致命的狀況、發生率約為每1000名活產嬰兒有2例。
  
  瑞典斯德哥爾摩Karolinska Institutet的Helle Kieler博士表示,懷孕後期服用SSRI的婦女生下的嬰兒,發生持續肺高壓的風險是沒有服用SSRI者產下之嬰兒的2倍。
  
  Kieler博士指出,絕對風險是曝露的嬰兒每1,000名有3例,增加的風險程度不論是整類的SSRI或者是特定的SSRI(sertraline、citalopram、paroxetine與fluoxetine)都是相似的。
  
  這篇研究線上登載於1月12日的英國醫學期刊。
  
  Christina D. Chambers醫師等人在2006年發表於新英格蘭醫學期刊的研究中提出風險達6倍,但是,該研究並未敘明特定物質,因為研究樣本有限,曝露於抗憂鬱藥物的嬰兒數太少。
  
  這促成了後續的研究,Kieler博士等人分析了丹麥、芬蘭、冰島、挪威、瑞典的全國出生登記資料,他們的分析包括了在1996-2007年間妊娠33週後產下的1,618,255 名單胞胎。
  
  他們根據藥物領用資料確認哪些婦女有使用SSRI,發現11,014名(0.7%)婦女曾在懷孕後期領用含一種SSRI的處方,有17,053人(1.1%)曾在懷孕初期領用含一種SSRI的處方;領用這類處方的媽媽們一般比較年長且有抽菸。
  
  研究發現另外54,184名孕婦曾有精神科診斷,但是懷孕期間並未用藥。
  
  研究顯示,懷孕後期曝露於SSRI的11,014名嬰兒中,33人診斷有持續的肺高壓。
  
  僅在懷孕初期曝露的17,053名嬰兒中,32人有持續肺高壓,曾有精神科診斷的母親中,114名嬰兒診斷有持續肺高壓;懷孕後期曝露於SSRI的風險較校正勝算比(AOR)為2.1 (95%信心區間[CI],1.5 - 3.0)。
  
  此外,懷孕初期曾領用含一種SSRI的婦女,其產下的嬰兒有40%風險(初期指妊娠第8週前;AOR,1.4;95% CI,1.0 - 2.0)。
  
  妊娠年齡小與剖腹產並不會影響新生兒發生持續肺高壓的可能性。
  
  Kieler博士表示,SSRI如何引起或促使持續肺高壓的機轉還未知。她認為,SSRI會在肺中累積,另外,其研究結果認為是SSRI類藥物的影響,而其他血清素和正腎上腺素類抗憂鬱藥物的風險也增加,或許這是血清素效應,血清素會引起血管收縮與調節肺動脈平滑肌細胞增生。
  
  Kieler博士表示,現在,醫師們應告知他們的病患有關風險增加的資訊,以及該疾病的發生率。
  
  我們建議應小心使用SSRI治療孕婦,懷孕期間盡可能考量非藥物的抗憂鬱治療。
  
  加拿大多倫多大學兒童醫院Motherisk計畫主任Gideon Koren醫師,與挪威奧斯陸大學的Hedvig Nordeng藥學博士在編輯評論中寫道,藥物流行病學研究可以顯示關聯性,但是無法證明因果關係。
  
  他們也指出,這篇研究的主要挑戰是依賴處方資料庫的資訊,必須證明這些處方都有被確實服用。
  
  編輯們表示,最近的一篇研究顯示,許多憂鬱婦女在懷孕期間並未服用她們的抗憂鬱藥物。Kieler博士等人的研究中,曝露的時機是根據藥局的調劑資料、定義的每日劑量(這可能和處方劑量有所差異),但是並未提及曝露時機的不確定性,也未提及如何計算。
  
  他們也問道,目前研究發現的關聯是否可以用母親原本的憂鬱症情況來解釋,而不是使用SSRI。
  
  Koren 醫師和Nordeng博士結論表示,後續研究、或者Kieler醫師等人的大型世代的後續分析,可能可以驗證這個風險、或者尚有不足。
  
  資料來源:http://www.24drs.com/professional/list/content.asp?x_idno=6709&x_classno=0&x_chkdelpoint=Y
  

SSRIs in Pregnancy Linked to Lung Hypertension in Newborns

By Fran Lowry
Medscape Medical News

January 13, 2012 — Pregnant women who take selective serotonin reuptake inhibitors (SSRIs) may be putting their babies at heightened risk of developing persistent pulmonary hypertension, a life-threatening condition that occurs in up to 2 per 1000 liveborn infants, according to new research.

Infants born to women treated with SSRIs in late pregnancy had a 2-fold increased risk for persistent pulmonary hypertension compared with infants born to women who did not use SSRIs, lead author Helle Kieler, MD, PhD, from the Karolinska Institutet, Stockholm, Sweden, and colleagues report.

"The absolute risk was 3 infants per 1,000 exposed, and the increased risk seemed to be a class effect of SSRIs, as risks for the specific SSRIs — sertraline, citalopram, paroxetine, and fluoxetine — were of similar magnitude," Dr. Kieler told Medscape Medical News.

The study is published online January 12 in the British Medical Journal.

Mechanism Unclear

An earlier study by Christina D. Chambers, MD, and colleagues, published in the New England Journal of Medicine in 2006, showed a 6-fold increased risk, but that study did not address specific substances because the study sample was limited, with too few infants exposed to the antidepressants, she said.

Prompted to study the issue further, Dr. Kieler and her team analyzed national birth registers in Denmark, Finland, Iceland, Norway, and Sweden. Their analysis included 1,618,255 singleton births born after gestational week 33 from 1996 to 2007.

They identified women exposed to SSRIs by linking with the drug registers on filled prescriptions. They found that 11,014 (0.7%) of the mothers had filled a prescription for an SSRI during late pregnancy, and 17,053 (1.1%) of the mothers had filled a prescription for an SSRI in early pregnancy only.

Mothers who filled a prescription were generally older and also smoked.

Another 54,184 mothers were found to have had a previous psychiatric diagnosis but were not on any medication during their pregnancy.

The study showed that 33 of the 11,014 infants exposed to an SSRI in late pregnancy had a diagnosis of persistent pulmonary hypertension.

Of the 17,053 infants exposed only in early pregnancy, 32 had persistent pulmonary hypertension of the newborn. Among the mothers who had a previous psychiatric diagnosis, 114 infants had a diagnosis of persistent pulmonary hypertension of the newborn.

The adjusted odds ratio (AOR) of risk after exposure to an SSRI in late pregnancy was 2.1 (95% confidence interval [CI], 1.5 - 3.0).

Additionally, there was a 40% risk for infants of women who filled a prescription with an SSRI in early pregnancy (before gestational week 8; AOR, 1.4; 95% CI, 1.0 - 2.0).

Small gestational age and Cesarean delivery did not influence the likelihood of having a newborn with persistent pulmonary hypertension.

The mechanism of how SSRIs would cause or promote persistent pulmonary hypertension in a newborn is unknown, Dr. Kieler said.

"SSRIs accumulate in the lungs," she suggested. "Also, considering our results suggesting a class effect for SSRIs and increased risks with other antidepressants with selectivity for serotonin and norepinephrine, one might suspect a serotonin effect. Serotonin can induce vasoconstriction and mediate pulmonary arterial smooth muscle cell proliferation."

For now, doctors should tell their patients about the increased risk but also about the rarity of the disease, Dr. Kieler said.

"We recommend caution when treating pregnant women with SSRIs and to consider nonmedical treatment for depression during pregnancy whenever possible."

Causation Difficult to Prove

Writing in an accompanying editorial, Gideon Koren, MD, director of the Motherisk Program at the Hospital for Sick Children, University of Toronto, Toronto, Canada, and Hedvig Nordeng, MSc, PharmD, from the University of Oslo, Oslo, Norway, note that pharmacoepidemiological studies can show an association but cannot prove causation.

They also point out that a major challenge in studies that rely on prescription database information is to prove that the prescriptions were in fact taken.

"A recent study showed that many women with depression did not take their prescribed antidepressants during pregnancy. In Kieler and colleagues’ study the timing of exposure was based on the pharmacies’ date of dispensing and defined daily dosages (which may differ from the prescribed doses), but they did not mention the uncertainty around the timing of exposure and how it was calculated," the editorialists observe.

They also ask whether the associations found in the current study can be explained by the underlying depression of the mother rather than use of SSRIs.

"Future studies, or additional analyses of Kieler and colleagues’ large cohort, may be able to quantify this risk, or the lack of one," Dr. Koren and Dr. Nordeng conclude.

The study was funded by the Swedish Pharmacy Company. Dr. Kieler, Dr. Koren, and Dr. Nordeng report no relevant financial relationships.

BMJ. Published online January 12, 2012.

    
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