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作者：Nancy Fowler Larson  
出處：WebMD醫學新聞

　　December 22, 2009 — 根據一項發表於12月21日線上兒科期刊上的研究結果，母親使用低劑量Aspirin（LDA）並不會對早產兒造成負面影響，且在兒童時期發生神經行為異常的機會可能更低。
　　
　　法國盧倫大學醫院新生兒醫學以及法國盧倫盧倫大學生化研究機構的St?phane Marret醫師與其同事們寫到，胎兒對Aspirin的耐受性良好，看起來可以降低好幾種不同的風險（包括子癲前症、37週前早產、以及胎兒生長限制），且不會增加嬰兒出血風險。然而，Aspirin對早產兒長期作用仍然未知。
　　
　　為了確認LDA對早產兒同的影響，研究者們針對於1997年656位33週出生在法國的兒童進行研究。新生兒的資料從Etude Epidemiologique des Petites Ages Gestationnels（EPIPAGE）世代研究收集而來。5年後，研究者們檢驗兒童發生腦性麻痺、行為問題與認知能力的發生率。
　　
　　研究者的結論是，LDA與長期預後之間並無顯著關係。除此之外，他們報告LDA與行為困難度降低有關。
　　
　　研究作者們寫到，接受LDA治療，5歲時腦性麻痺的比例並無差異，低MPC（精神運作複合分數）、低序列運算分數（<70分）機率同樣沒有差異。LDA組同時運算分數低於70分的比例顯著低於非LDA組（7%相較於19%；P=0.04），但是在校正PS（傾向評分）、預後因子與社會經濟地位（校正勝算比[aOR]為0.59[95%信賴區間（CI）為0.17-2.06]）後並非如此。研究結果顯示，與LDA治療相關的整體行為困難（aOR為0.44[95% CI：0.19-1.02]）與（aOR為0.43[95% CI：0.17-1.05]）在校正PS與預後因子後下降到顯著差異下限。
　　
　　加州史丹佛大學醫學院兒童新生兒學教授Vinod Bhutani醫師在訪談中表示，未來需要針對不同族群，以及懷孕週數少於28週出生的嬰兒進行更多研究。除此之外，Bhutani醫師評論該項研究的作者們研究細心，且稱這項研究發現有重大貢獻。
　　
　　Bhutani醫師表示，Aspirin對心臟疾病與微血管疾病的效果是很奇妙的，且這顯示這在懷孕時期使用具有潛力。
　　
　　但是，德州休士頓貝勒醫學院的小兒科教授LuAnn Papile醫師發現這項研究有許多瑕疵，包括樣本數目少以及資料遺失。根據Papile醫師表示，這些發現讓我們對其結論產生疑問，包括LDA是無害的，且這個藥物對於神經行為可能有好處。
　　
　　Papile醫師在訪談中表示，他們僅有61%兒童的認知分數以及69%兒童的行為分數。對大部分的後續追蹤研究來說，85%是區間值。他們的結論真的有待證實。
　　
　　研究作者們承認確實有許多限制，包括25%兒童並未在5歲時接受評估。他們也宣稱控制組相較於LDA部分未後續追蹤的比例較高，這可能造成非LDA組神經發展受損被低估。
　　
　　研究者們指出，他們相信這項研究是第一項仔細檢查LDA在這同質性高新生兒族群所造成影響的研究。但是，他們提醒在進一步研究結果公布前，反對將他們的發現應用在臨床上。
　　
　　研究作者們寫到，這些研究結果應該小心闡釋且需要加以確認。目前急迫地需要其他研究來確認懷孕時使用aspirin的臨床潛力，因為這些病患並沒有太多神經保護藥物可以使用。
　　
　　INSERM（國家健康與醫學研究機構）、健康照護署社會事務綜合部門、Merck-Sharp與Dhome-Chibret、醫學研究基金會、HAS（法國健康管理當局）、法國衛生部門臨床研究醫院計劃2001（AOMO1117）贊助這項研究。試驗研究作者表示已無相關資金上的往來。


Low-Dose Aspirin During Pregnancy Has No Adverse Impact on Preterm Infants

By Nancy Fowler Larson
Medscape Medical News

December 22, 2009 — Preterm infants whose mothers took low-dose aspirin (LDA) exhibit no negative long-term effects and may have fewer neurobehavioral difficulties as children, according to a study published online December 21 in Pediatrics.

"Aspirin is well tolerated by the fetus and seems to produce a moderate reduction of several different risks (preeclampsia, delivery before 37 weeks of gestation, and fetal growth restriction) without increasing infant bleeding," write Stephane Marret, MD, PhD, Department of Neonatal Medicine, Rouen University Hospital, Rouen, France, and the Institute for Biomedical Research, Rouen University, Rouen, France, and colleagues. "Nevertheless, the long-term effects of aspirin on preterm children are unknown."

To determine the effects of LDA on preterm children, researchers studied 656 children born in France in 1997 before 33 weeks' gestation. Newborn data were gathered from the Etude Epidemiologique des Petites Ages Gestationnels (EPIPAGE) cohort study, which primarily measured mortality and cerebral lesions. Obstetric records confirmed LDA intake. After 5 years, the investigators examined the children for incidence of cerebral palsy, behavioral issues, and cognitive ability.

Researchers concluded there was no significant relationship between LDA and any long-term outcome. Furthermore, they reported an association of LDA with a decrease in behavioral difficulties.

"The cerebral palsy rate at 5 years of age did not differ according to LDA treatment nor did the rate of low MPC [mental processing composite] or low sequential processing scores (<70). The rate of simultaneous processing scores of <70 was significantly lower in the LDA group than in the no-LDA group (7% vs 19%; P = .04), but not after adjustment for PS [propensity score], prognostic factors, and social class (adjusted odds ratio [aOR]: 0.59 [95% confidence interval (CI): 0.17–2.06])," the study authors write. "Results showed a reduction at the limit of significance in total behavioral difficulties (aOR: 0.44 [95% CI: 0.19 –1.02]) and hyperactivity (aOR: 0.43 [95% CI: 0.17–1.05]) associated with LDA treatment after adjustment for PS and prognostic factors."

Vinod Bhutani, MD, FAAP, professor of pediatrics-neonatology, Stanford University School of Medicine, Stanford, California, noted in an interview that further research is needed on more diverse populations and in infants of less than 28 weeks' gestation. Still, Dr. Bhutani commended the study authors for their "meticulous work" and called the findings a "major contribution."

"Aspirin has done wonders in heart disease and microvascular disease and this shows it has a potential future for use during pregnancy," Dr. Bhutani said.

But LuAnn Papile, MD, professor of pediatrics, Baylor College of Medicine, Houston, Texas, found numerous flaws in the study, including low numbers and missing data. According to Dr. Papile, these failings cast doubt on both conclusions — that LDA causes no harm and that it may benefit neurologic behavior.

"They only have cognitive scores on 61% and behavioral scores on only 69% of the children. For most follow-up studies, 85% is the cutoff," Dr. Papile said in an interview. "Their conclusions are truly unwarranted."

The study authors acknowledged several limitations, including the fact that 25% of the children were not evaluated as 5-year-olds. They also stated that the rate of loss to follow-up was higher in the control group vs the LDA faction, which "may have resulted in an underestimation of neurodevelopmental impairments in the no-LDA group."

The researchers pointed out that they believe this study is the first to scrutinize the impact of LDA in such a homogeneous newborn population. But they warned against implementation of their findings pending further research.

"However, these results should be interpreted with caution and need to be confirmed," the study authors write. "Other studies are urgently needed to confirm the clinical potential of aspirin use during pregnancy, because few neuroprotective agents have been identified."

INSERM (National Institute of Health and Medical Research), the Directorate General for Health of the Ministry for Social Affairs, Merck-Sharp and Dhome-Chibret, Medical Research Foundation, HAS (French National Authority for Health), and the Hospital Program for Clinical Research 2001 (AOMO1117) of the French Ministry of Health supported this study. The study authors have disclosed no relevant financial relationships.

Pediatrics. Published online December 21, 2009.