【作者】 黄昕；

【导师】 谭红专；

【作者基本信息】 中南大学 ， 流行病与卫生统计学， 2010， 博士

【摘要】 目的：研究第一胎剖宫产与第二胎单胎新生儿患病和死亡的关系。根据研究结果为卫生政策的制定提供参考意见,以及为临床工作提供参考依据。方法：采用美国国家卫生统计中心(NCHS)公布的1995年-2002年度出生死亡链接资料,选取在1995年1月1日至2002年12月31日期间,于美国本土50个州和哥伦比亚特区出生的全部第二胎单胎活产新生儿进行历史性队列研究。根据第一胎的分娩方式将研究人群分为既往剖宫产和既往自然分娩两组,比较这两组人群中第二胎新生儿的机械通气使用、第5分钟Apgar评分低于7分、急性胎儿窘迫、惊厥、早产、大于孕周儿(LGA)、小于孕周儿(SGA)、新生儿全死因死亡和缺氧相关死亡发生情况的差异。为了控制某些能够影响第二胎分娩方式的因素,依据孕妇的疾病史和既往分娩史情况进行分层,同时探讨孕期疾病和不良分娩史对第一胎剖宫产与第二胎新生儿不良结局之间相关性的影响。将孕产妇的社会人口学特征包括母亲的年龄、种族、早孕期保健开展的情况、受教育年限、孕期吸烟情况和新生儿性别作为协变量,采用Poisson多因素模型分别估计第一胎剖宫产与第二胎新生儿的机械通气使用、第5分钟Apgar评分低于7分急性胎儿窘迫、惊厥、早产、LGA、SGA、新生儿全死因死亡、新生儿缺氧相关死亡之间的调整RR值。本研究同时选取了母亲种族为华裔的人群来探讨第一胎剖宫产与各种新生儿患病、死亡与既往剖宫产之间的关系在华裔亚组人群中是否与全研究人群相似,关联是否存在一致性。结果：1)一般情况：1995年至2002年期间,在美国本土50个州和哥伦比亚特区出生的活产儿共有31,679,722人,其中符合本研究纳入标准的第二胎、单胎、孕24-44周、体重500-6500克的活产儿共有9,643,175人。1995年至2002年期间,美国本土地区第二胎单胎的剖宫产平均使用率为21.14%,呈逐年上升趋势。同时新生儿机械通气的使用和早产率总体呈现上升趋势,分别从23.1‰和8.6%上升至25.4‰和9.4%；新生儿第5分钟Apgar评分低于7分发病率、惊厥发病率、急性窘迫发病率、LGA发病率、SGA发病率、新生儿死亡率分别从8.9‰,0.8‰,32.6‰,11.6%,8.9%,2.1‰下降至7.7‰,0.4‰,27.1‰,10.9%,8.7%,1.8‰,呈现出具有统计学意义的整体下降趋势。根据母亲第一胎的分娩方式将人群分为既往剖宫产组和既往自然分娩组,与既往自然分娩组相比,在生育第二胎时既往剖宫产组产妇年龄偏大,已婚人士居多,接受16年以上教育年限的人口比例更多,非西班牙裔白种人的比例更高,孕期吸烟率更低,更有可能在早孕期就开展孕期保健。同时,既往剖宫产组母亲孕期心脏疾病、急慢性肺病、糖尿病、慢性高血压、肾脏疾病患病率,以及有既往早产儿或SGA儿生育史的比例,均高于既往自然分娩组。2)全人群中既往剖宫产与各种新生儿结局：在全部样本人群中,第一胎剖宫产与第二胎新生儿人工机械通气、第5分钟Apgar评分低于7分、、惊厥、急性胎儿窘迫、早产、LGA、SGA、新生儿全死因死亡和缺氧相关死亡的粗RR值分别为1.47(95%CI：1.46,1.49),]1.14(95%CI：1.12,1.17),1.36(95%CI：1.27,1.45),1.46(95%CI：1.44,1.47),1.00(95%CI：0.99,1.00),1.32(95%CI：1.32,1.33),0.95(95%CI：0.92,0.93),1.0l(95%CI：0.98,1.04)和1.56(95%CI：1.38,1.72)。根据母亲孕期是否具有疾病或不良分娩史,将研究人群分为‘健康’和‘非健康’人群。孕期疾病或不良分娩史对第一胎剖宫产与第二胎新生儿第5分钟Apgar评分低于7分、惊厥、SGA、新生儿全死因死亡、新生儿缺氧相关死亡的关联不存在修饰效应。而第一胎剖宫产与第二胎新生儿人工机械通气、急性胎儿窘迫、早产和LGA之间的关联受母亲孕期疾病或不良分娩史的修饰作用。第一胎剖宫产与第二胎新生儿Apgar得分低于7分、惊厥、新生儿缺氧相关死亡之间的关联在经过对孕产妇的年龄、种族、早孕期保健开展的情况、受教育年限、孕期吸烟情况、母亲孕期疾病、不良分娩史情况以及第二胎胎儿的性别、早产因素调整后仍具有统计学意义,调整RR值分别为1.13(95%CI：1.11,1.15),1.36(95%CI：1.27,1.46)和1.52(95%CI：1.36,1.71)。第一胎剖宫产与第二胎新生儿全死因死亡之间不存在具有统计学意义的关联(调整RR=1.03,95%CI：0.99,1.07)。第一胎剖宫产与第二胎新生儿SGA之间的调整RR值为0.98(95%CI：0.98,0.99)。考虑到孕期疾病或不良分娩史的修饰作用,我们在‘健康’和‘非健康’人群中分别估计既往剖宫产与人工机械通气、急性胎儿窘迫、早产、LGA的调整RR值。研究发现,虽然既往剖宫产与人工机械通气、急性胎儿窘迫、LGA之间的关联性受母亲孕期疾病或不良分娩史的修饰作用,然而该关联在两层亚组人群中均具有统计学意义。在‘健康人群’中,既往剖宫产与人工机械通气、急性胎儿窘迫、LGA的调整RR值分别为1.43(95%CI：1.42,1.45),1.43(95%CI：1.42,1.44)和1.29(95%CI：1.28,1.30)；在‘非健康人群’中的调整RR值,分别为1.39(95%CI：1.35,1.43),1.11(95%CI：1.09,1.14)和1.58(95%CI：1.56,1.61)。既往剖宫产与第二胎早产之间的关联性在‘健康人群’和‘非健康人群’中则表现出不同的关联程度。在‘健康人群’中,既往剖宫产与第二胎早产不存在具有统计学意义的关联(调整RR=1.00,95%CI：0.99,1.00)；在‘非健康人群’中,既往剖宫产与早产则表现出具有统计学意义的关联,调整RR值为1.03(95%CI：1.02,1.05)。3)华裔人群中既往剖宫产与新生儿结局：在调整了母亲社会人口学资料、孕期吸烟、早孕期保健情况、疾病史和既往分娩史的资料后,在华裔人群中,新生儿机械通气、急性胎儿窘迫、早产、LGA、SGA与既往剖宫产之间的关系与全人群的的研究结果保持一致,调整RR值分别为1.52(95%CI：1.30,1.77),1.75(95%CI：1.56,1.97),1.06(95%CI：0.99,1.14),1.43(95%CI：1.34,1.53)和0.86(95%CI：0.80,0.93)。惊厥、新生儿缺氧相关死亡与既往剖宫产之间的关联性在该亚组人群的结果与全人群结果不同,其关联没有统计学意义。结论：第一胎剖宫产能增加第二胎新生儿机械通气使用、第5分钟Apgar得分低于7分、惊厥、发生急性胎儿窘迫、LGA及缺氧相关死亡的危险性,并且该关联不完全由母亲疾病史和不良分娩史所导致。既往剖宫产史与孕期母亲具有合并症或既往不良分娩史同时存在的情况下,既往剖宫产才能增加第二胎新生儿发生早产的危险性。在华裔亚组人中,同样观察到第一胎剖宫产的使用能增加第二胎新生儿机械通气使用、发生急性胎儿窘迫、早产和LGA的危险性。研究结果提示临床医生以及病人要共同慎重地决定第一胎剖宫产分娩,尤其是在没有明确剖宫产指症的情况之下。更多还原

【Abstract】 Objectives:To examine the independent impact of cesarean delivery in first pregnancy on neonatal mortality and morbidity in second pregnancy. This study was designed to provide evidence for clinical work and give some advise for decision-making on health strategy.Methods:A retrospective cohort study was conducted, based on the 1995-2002 linked live birth/infant death registration data of the United States compiled by the National Center for Health Statistics, Centers for Disease Control and Prevention. The linked registration data were based on all live births and infant deaths up to 1 year, registered in the 50 states and the District of Columbia. All of the study subjects were classified into two groups according to mode of delivery in first pregnancy:caesarean delivery in first pregnaney and vaginal delivery in first pregnancy. The prevalence rate of assisted ventilation,5 minutes Apgar score lower than 7, fetal distress, seizure, preterm, large for gestational age(LGA), small for gestational age(SGA) and neonatal death were compared between those two groups. Stratified analysis was performed to control confounding by indication of second second birth and exam if maternal health problems have modifying effects on the association between previous delivery method and neonatal outcomes. Maternal age, race, prenatal care began time, education year, smoking and child sex were adopted as covariates and multiple Poisson regression were used to estimate the association of model of delivery in the first pregnancy with neonatal morbidity and mortality in the second pregnancy. A subgroup of mothers of ethnic Chinese were selected to test if association in this subgroup population was consistence with overall population.Results:1) General characteristics:There were 31,713,906 births in the 1995-2002 linked birth and infant death data. Among them, 9,643,175 were second, singleton, and live births born between 24-44 weeks of gestation, with birth weight between 500-6500 gram. During 1995 to 2002, the average cesarean rate was 21.14% and showed upward trend by years. In 1995, the assisted ventilation and preterm rate were 23.1‰and 8.6%, and climbed to 25.4‰and 9.4% separately in 2002. Meanwhile,5 minute Apgar score lower than 7, seizure, fetal distress, LGA, SGA rate and neonatal mortality rate were declined from 8.9‰, 0.8‰,32.6‰,11.6%,8.9%,2.1‰to 7.7‰,0.4‰,27.1‰,10.9%,8.7%, 1.8‰separately, which showed statistical meaningful downward trend by years. According to the mode of delivery in first pregnancy, all of the study subjects were classified into two groups:previous cesarean delivery group and previous vaginal delivery group. Compared with previous vaginal delivery group, mothers with previous cesarean delivery tended to be older, married, non-Hispanic white, starting their prenatal care in first trimester, with higher education level, less tobacco usage during pregnancy and more likely being with medical complication in second pregnancy or adverse birth history in first pregnancy.2) Association between previous cesarean section and neonatal outcomes in overall population:The crude Risk Ratio for previous cesarean section and subsequent neonatal assisted ventilation,5 min Apgar score< 7, seizure, fetal distress, preterm, LGA, SGA, All-cause neonatal death, Asphyxia-related neonatal death were 1.47(95%CI:1.46, 1.49),1.14(95%CI:1.12,1.17),1.36(95%CI:1.27,1.45),1.46(95%CI: 1.44,1.47),1.00(95%CI:0.99,1.00),1.32(95%CI:1.32,1.33), 0.95(95%CI:0.95,0.96),1.01(95%CI:0.98,1.04)and 1.56(95%CI:1.38, 1.72) separately.According to the maternal medical complication and adverse birth history, we stratified all of the study subjects into ’healthy’ and ’unhealthy’ layer. We found that the association between subsequent neonatal 5 min Apgar score< 7, seizure, SGA, All-cause neonatal death, Asphyxia-related neonatal death and previous cesarean section were not modified by maternal medical complication or adverse birth history in first pregnancy. However, the association between assisted ventilation, fetal distress, preterm, LGA and previous cesarean section were all modified by maternal medical complication and adverse birth history.After the adjustment for maternal age, race, prenatal care began time, year of education, smoking, infant sex, preterm, maternal medical complication and adverse birth history in first pregnancy, the association between subsequent neonatal 5 min Apgar score< 7, seizure, Asphyxia-related neonatal death and previous cesarean section still exist and the adjusted Risk Ratio were 1.13 (95%CI:1.11,1.15),1.36 (95%CI: 1.27,1.46) and 1.52 (95%CI:1.36,1.71) separately. The relationship between All-cause neonatal death and previous C-section is statically insignificant (adjusted RR=1.03,95%CI:0.99,1.07). The adjusted Risk Ratio for SGA and previous C-section is 0.98(95%CI:0.98,0.99).After considering the modification effects of maternal medical or adverse birth history, we estimated the association between previous cesarean delivery and assisted ventilation, fetal distress, preterm, LGA in two layers separately. Compared with previous vaginal delivery group, infants born to mothers with a previous cesarean delivery had higher rates of assisted ventilation, fetal distress and LGA in both layers:in ’unhealthy’layer, the adjusted Risk Ratio for previous cesarean and ventilation, fetal distress were 1.43(95%CI:1.42,1.45),1.43(95%CI: 1.42,1.44) and 1.29(95%CI:1.28,1.30) separately; in ’healthy’ layer, the adjusted Risk Ratio were 1.39(95%CI:1.35,1.43),1.11(95%CI: 1.09,1.14) and 1.58(95%CI:1.56,1.61) separately.The association between preterm and previous cesarean section showed different strength. Previous cesarean delivery is not associated with preterm in’healthy’layer (adjusted RR=1.00,95%CI:0.99,1.00), but has statistical association with preterm in’unhealthy’layer (adjusted RR=1.03,95%CI:1.02,1.05).3) Association between previous cesarean section and neonatal outcomes in Chinese subgroup population:After the adjustment of maternal age, race, prenatal care began time, year of education, smoking, infant sex, preterm, maternal medical complication and adverse birth history in first pregnancy, the relationship between assisted ventilation, fetal distress, preterm, LGA, SGA and previous cesarean delivery in Chinese race subgroup are consistence with overall population, the Risk Ratio were 1.52(95%CI:1.30,1.77),1.75(95%CI:1.56,1.97), 1.06(95%CI:0.99,1.14),1.43(95%CI:1.34,1.53) and 0.86(95%CI:0.80, 0.93) separately. The association between seizure, asphyxia-related neonatal death and previous cesarean delivery are statistically insignificant in Chinese race subgroup, which is different from overall population. Compared with previous vaginal delivery group, infants bom to mothers with a previous cesarean delivery had lower risk of having SGA infant in second pregnancy, which is consistent with the association in’healthy’layer.Conclusions:Compared with previous vaginal delivery group, infants born to mothers with a previous cesarean delivery had higher rates of assisted ventilation,5 minte Apgar score lower than 7, seizure, fetal distress and LGA. Those relationships are not all contributed to maternal medical complication or adverse birth history. Previous cesarean delivery is associated with preterm in second pregnancy only among those with maternal medical complication or adverse birth history population. In Chinese race subgroup population, the relationship between assisted ventilation, fetal distress, preterm, LGA and previous cesarean delivery still exist. Clinicians should be cautious on a decision for cesarean delivery, especially those when there is no clear medical indication for cesarean section.更多还原