對(duì)乙酰氨基酚與出生缺陷

1、孕期應(yīng)用(yngyng)對(duì)乙酰氨基酚與出生缺陷的風(fēng)險(xiǎn)Findings From the National Birth Defects Prevention StudyMarcia L. Feldkamp, PhD, Robert E. Meyer, PhDVOL. 115, NO. 1, JANUARY 2010共二十頁(yè)To investigate whether exposure during the first trimester of pregnancy to single-ingredient acetaminophen increases the risk of major birt

2、h defects.共二十頁(yè)The usual recommended dose of acetaminophen is close to its toxic adult dose (the therapeutic index is narrow), raising concern for maternal overdose and fetal toxicity (對(duì)乙酰氨基酚90%95%在肝臟代謝.每天總量不超過(guò)2克，是安全的。若每天服用該藥的總量超過(guò)4克，則可致肝損害；大于10克，患者(hunzh)有可能因肝衰竭而死亡。)共二十頁(yè)A recent study found that 65.5

3、% of women reported its use sometime during pregnancy, and 54.2% used acetaminophen during the first trimester.共二十頁(yè)Fetal growth and adverse birth outcomes in women receiving prescriptions for acetaminophen during pregnancy. Thulstrup AM, Srensen HTet al. Am J Perinatol 1999;16:3216.共二十頁(yè)Acetaminophen

4、 use during pregnancy:effects on risk for congenital abnormalities. Rebordosa C, Kogevinas M, Am J Obstet Gynecol 2008;198:178.e17共二十頁(yè)Women who delivered between January 1,1997, and December 31, 2004, and participated in the telephone interview were included.Children were included in the case or con

5、trol groups if they were born after October 1, 1997, and had an estimated date of delivery (EDD) before January 1, 2005共二十頁(yè)共二十頁(yè)The case group includes live births, stillbirths, and pregnancy terminations with selected birth defects identified through population-based birth-defect registries. Those i

6、n the case group with a known cause for the birth defect (eg,chromosomal or genetic disorders) are excluded. Participants for the control group are selected randomly from all live births to represent the case population of each center共二十頁(yè)1997.10.1-2005.1.1出生(chshng)的兒童總數(shù)應(yīng)用時(shí)間不確定應(yīng)用復(fù)合制劑孕前糖尿病確定研究總數(shù)受試組15

7、778274967274711610對(duì)照組595810842261484500共二十頁(yè)評(píng)估出生(chshng)缺陷患兒風(fēng)險(xiǎn)變量1、maternal age (younger than 20 years, 2024 years,2529 years, 30 years or older)2、education (less than 12years, 12 years, more than 12 years),3、body mass index in kg/m2 (lower than 18.5, 18.524.9,25.029.9, 30.0 or higher),4、 gestational

8、diabetes (yes, no),5、fever (yes, no), 6、smoking in the first trimester (yes, no),7、folic acid use from 3 months before conception through8、the first trimester (none, intermittent or less than 12 days per month, and continuous or 12 or more days per month),9、 race/ethnicity (non-Hispanic white, non-H

9、ispanic African American, Hispanic, other)10、parity (0,1, 2, 3, 4 or more).共二十頁(yè)共二十頁(yè)單一成分對(duì)乙酰氨基酚使用率%受試組對(duì)照組p46.945.80.2120歲以下42.8370.0225-29歲49.448.3非西班牙裔白人55.355.9西班牙裔白人32.930.2共二十頁(yè)排除感染/高熱潛在危險(xiǎn)因素(yn s)的干擾women who reported no history of either infection or fever women who reported infection without feve

10、r women who reported infection and fever.共二十頁(yè)孕初期(chq)感染/高熱/對(duì)乙酰氨基酚Among mothers of children in the case and control groups reporting no infection or fever during the first trimester, both elevated and decreased ORs were seen, none of which were statistically significant (Fig. 2)first-trimester infect

11、ion without fever comparedwith those who reported neither infection nor fever (Fig.2, )Elevated ORs were observed among many phenotypes, but CIs included 1.0 in all but one phenotype: a statistically significantly decreased OR was observed for choanal atresia（鼻后孔閉鎖）both firsttrimester infection and

12、fever, the results were quite varied (Fig. 2)Significantly decreased ORs were seen for anencephaly or craniorachischisis, encephalocele, anotia or microtia, all oral facial clefts, cleft lip with or without cleft palate, and gastroschisis(先天無(wú)腦 脊柱(jzh)裂 腦膨出 無(wú)耳或小耳 口面裂 唇裂伴或不伴腭裂 腹裂)共二十頁(yè)OR1，表示該暴露因素與疾病(jb

13、ng)為正相關(guān)，暴露因素使疾病(jbng)發(fā)生的危險(xiǎn)性增加；OR1，表示暴露因素與疾病(jbng)為負(fù)相關(guān)，暴露因素對(duì)預(yù)防疾病(jbng)的發(fā)生有保護(hù)性作用；如果OR接近或等于1，說(shuō)明暴露與所研究的疾病(jbng)無(wú)關(guān)。共二十頁(yè)陰莖(ynjng)畸形膀胱(png gung)畸形神經(jīng)管畸形無(wú)腦兒脊柱裂腦膨出顱縫早閉小腦蚓部的缺乏 dandy-walker前腦無(wú)裂畸形 腦積水 無(wú)眼球癥 白內(nèi)障青光眼小耳畸形 后鼻孔閉鎖 口面裂唇裂不伴腭裂腭裂食管閉鎖 膽道閉鎖 腸閉鎖 先天性肛門(mén)閉鎖 先天性膈疝 臍膨出 腹裂 雙腎發(fā)育不全尿道下裂 骶骨發(fā)育不全 縱向肢體缺陷橫向肢體缺陷中層肢體缺陷上肢內(nèi)側(cè)肢體缺陷

14、羊膜帶畸形肢體壁綜合畸形縱向肢體缺陷橫向肢體缺陷中層肢體缺陷縱向肢體缺陷橫向肢體缺陷共二十頁(yè)圓錐(yunzhu)動(dòng)脈干畸形 完全性大動(dòng)脈轉(zhuǎn)位(zhun wi) 法洛四聯(lián)癥 左室流出道梗阻右室流出道梗阻左心發(fā)育不全綜合征主動(dòng)脈縮窄主動(dòng)脈瓣狹窄 肺動(dòng)脈閉鎖三尖瓣閉鎖 肺動(dòng)脈瓣狹窄 肺動(dòng)脈瓣狹窄綜合征 三尖瓣下移畸形 全肺靜脈回流異常 內(nèi)臟異位伴先天性心臟缺損 房室間隔缺損 中隔缺陷室中隔缺損 膜部室中隔缺損 肌性繼發(fā)性心房中隔缺損 共二十頁(yè)神經(jīng)管畸形(jxng)無(wú)腦兒脊柱(jzh)裂腦膨出小腦蚓部的缺乏 dandy-walker前腦無(wú)裂畸形 腦積水 無(wú)眼球癥 青光眼小耳畸形 后鼻孔閉鎖 白內(nèi)障顱縫

15、早閉口面裂唇裂不伴腭裂腭裂膽道閉鎖 腸閉鎖 先天性肛門(mén)閉鎖 膽道閉鎖 先天性膈疝 臍膨出 腹裂 陰莖畸形膀胱畸形雙腎發(fā)育不全尿道下裂 骶骨發(fā)育不全 縱向肢體缺陷上肢內(nèi)側(cè)肢體缺陷縱向肢體缺陷中層肢體缺陷縱向肢體缺陷橫向肢體缺陷羊膜帶畸形肢體壁綜合畸形圓錐動(dòng)脈干畸形 完全性大動(dòng)脈轉(zhuǎn)位 法洛四聯(lián)癥 左室流出道梗阻左心發(fā)育不全綜合征主動(dòng)脈縮窄主動(dòng)脈瓣狹窄 右心發(fā)育不全綜合征三尖瓣閉鎖 肺動(dòng)脈瓣狹窄 肺動(dòng)脈瓣狹窄綜合征 三尖瓣下移畸形 肺動(dòng)脈閉鎖全肺靜脈回流異常 內(nèi)臟異位伴先天性心臟缺損 房室間隔缺損 中隔缺陷室中隔缺損 膜部室中隔缺損 肌性繼發(fā)性心房中隔缺損 共二十頁(yè)內(nèi)容摘要孕期應(yīng)用對(duì)乙酰氨基酚。Thulstrup AM, Srensen HTet al.。Am J Perinatol 1999。Acetaminophen u