对乙酰氨基酚与出生缺陷

1、孕期应用(yngyng)对乙酰氨基酚与出生缺陷的风险Findings From the National Birth Defects Prevention StudyMarcia L. Feldkamp, PhD, Robert E. Meyer, PhDVOL. 115, NO. 1, JANUARY 2010共二十页To investigate whether exposure during the first trimester of pregnancy to single-ingredient acetaminophen increases the risk of major birt

2、h defects.共二十页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 (对乙酰氨基酚90%95%在肝脏代谢.每天总量不超过2克，是安全的。若每天服用该药的总量超过4克，则可致肝损害；大于10克，患者(hunzh)有可能因肝衰竭而死亡。)共二十页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.共二十页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.共二十页Acetaminophen

4、 use during pregnancy:effects on risk for congenital abnormalities. Rebordosa C, Kogevinas M, Am J Obstet Gynecol 2008;198:178.e17共二十页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共二十页共二十页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共二十页1997.10.1-2005.1.1出生(chshng)的儿童总数应用时间不确定应用复合制剂孕前糖尿病确定研究总数受试组15

7、778274967274711610对照组595810842261484500共二十页评估出生(chshng)缺陷患儿风险变量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).共二十页共二十页单一成分对乙酰氨基酚使用率%受试组对照组p46.945.80.2120岁以下42.8370.0225-29岁49.448.3非西班牙裔白人55.355.9西班牙裔白人32.930.2共二十页排除感染/高热潜在危险因素(yn s)的干扰women who reported no history of either infection or fever women who reported infection without feve

10、r women who reported infection and fever.共二十页孕初期(chq)感染/高热/对乙酰氨基酚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（鼻后孔闭锁）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(先天无脑 脊柱(jzh)裂 脑膨出 无耳或小耳 口面裂 唇裂伴或不伴腭裂 腹裂)共二十页OR1，表示该暴露因素与疾病(jb

13、ng)为正相关，暴露因素使疾病(jbng)发生的危险性增加；OR1，表示暴露因素与疾病(jbng)为负相关，暴露因素对预防疾病(jbng)的发生有保护性作用；如果OR接近或等于1，说明暴露与所研究的疾病(jbng)无关。共二十页阴茎(ynjng)畸形膀胱(png gung)畸形神经管畸形无脑儿脊柱裂脑膨出颅缝早闭小脑蚓部的缺乏 dandy-walker前脑无裂畸形 脑积水 无眼球症 白内障青光眼小耳畸形 后鼻孔闭锁 口面裂唇裂不伴腭裂腭裂食管闭锁 胆道闭锁 肠闭锁 先天性肛门闭锁 先天性膈疝 脐膨出 腹裂 双肾发育不全尿道下裂 骶骨发育不全 纵向肢体缺陷横向肢体缺陷中层肢体缺陷上肢内侧肢体缺陷

14、羊膜带畸形肢体壁综合畸形纵向肢体缺陷横向肢体缺陷中层肢体缺陷纵向肢体缺陷横向肢体缺陷共二十页圆锥(yunzhu)动脉干畸形 完全性大动脉转位(zhun wi) 法洛四联症 左室流出道梗阻右室流出道梗阻左心发育不全综合征主动脉缩窄主动脉瓣狭窄 肺动脉闭锁三尖瓣闭锁 肺动脉瓣狭窄 肺动脉瓣狭窄综合征 三尖瓣下移畸形 全肺静脉回流异常 内脏异位伴先天性心脏缺损 房室间隔缺损 中隔缺陷室中隔缺损 膜部室中隔缺损 肌性继发性心房中隔缺损 共二十页神经管畸形(jxng)无脑儿脊柱(jzh)裂脑膨出小脑蚓部的缺乏 dandy-walker前脑无裂畸形 脑积水 无眼球症 青光眼小耳畸形 后鼻孔闭锁 白内障颅缝

15、早闭口面裂唇裂不伴腭裂腭裂胆道闭锁 肠闭锁 先天性肛门闭锁 胆道闭锁 先天性膈疝 脐膨出 腹裂 阴茎畸形膀胱畸形双肾发育不全尿道下裂 骶骨发育不全 纵向肢体缺陷上肢内侧肢体缺陷纵向肢体缺陷中层肢体缺陷纵向肢体缺陷横向肢体缺陷羊膜带畸形肢体壁综合畸形圆锥动脉干畸形 完全性大动脉转位 法洛四联症 左室流出道梗阻左心发育不全综合征主动脉缩窄主动脉瓣狭窄 右心发育不全综合征三尖瓣闭锁 肺动脉瓣狭窄 肺动脉瓣狭窄综合征 三尖瓣下移畸形 肺动脉闭锁全肺静脉回流异常 内脏异位伴先天性心脏缺损 房室间隔缺损 中隔缺陷室中隔缺损 膜部室中隔缺损 肌性继发性心房中隔缺损 共二十页内容摘要孕期应用对乙酰氨基酚。Thulstrup AM, Srensen HTet al.。Am J Perinatol 1999。Acetaminophen u