高龄与死胎

二胎政策的全面放开及辅助生殖技术的开展,使我国高龄妊娠妇女越来越多,高龄妊娠易合并多种内外科疾病,并发胎儿宫内发育异常、胎儿染色体疾病、胎死宫内等,导致不良妊娠结局。临床上应加强对高龄妊娠妇女的监护,规范产前检查、重点筛查、早期诊断、及时治疗、适时终止妊娠,降低不良妊娠结局的发生率,文章就高龄与死胎的关系、高龄导致死胎的机制以及如何预防死胎改善妊娠结局进行论述。     

彩色多普勒超声在预测死胎中的作用

死胎是指妊娠大于23+6周、无生命迹象的胎儿,是围产儿死亡的主要原因之一,产前有效预测死胎,对降低围产儿死亡率具有重大意义。利用彩色多普勒超声监测不同孕期母体子宫动脉血流参数,特别是妊娠中期子宫动脉搏动指数(PI)对与子痫前期、胎盘早剥、小于胎龄儿(SGA)相关的死胎预测有重要意义;监测胎儿各项多普勒血流参数,如脐动脉、大脑中动脉、静脉导管、腹内脐静脉等,能够反映胎儿宫内缺氧状况,提高胎儿窘迫的诊断率;联合监测母体及胎儿各项血流参数,全面评估胎儿宫内缺氧程度并及时干预,可避免死胎的发生。     

死胎病因及处理的最新循证医学证据

死胎(fetal death)是指胎儿在娩出前死亡,娩出时无任何生命迹象,包括无呼吸、无心跳、无脐动脉搏动或自主肌运动.早期死胎指死胎体重≥500 g或妊娠满22周或身长≥25 cm.晚期死胎指死胎体重≥1000 g或妊娠满28周或身长≥35 cm,体重较孕周更优先考虑[1].不同国家和地区有关死胎孕周和体重的定义不同.为便于统计和比较,世界卫生组织(World Health Organization,WHO)规定,妊娠满28周,出生体重≥1000 g诊断死胎[2];美国妇产科医师学院(American College of Obstetricians and Gynecologists,ACOG)规定妊娠满20周,出生体重≥350 g诊断死胎[3].     

预防死胎的临床监测方法

我国界定死胎为妊娠20周后临产前的胎儿死亡称为死胎。死胎发生率的高低直接影响围产儿死亡率,而后者是评估一个国家和地区医疗质量的敏感指标。临床上死胎发生前后常有迹可循。正确识别高危因素,加强孕期管理,有效利用检测手段是预防死胎发生,提高产科质量的关键。     

116例孕晚期死胎临床分析

目的:分析孕晚期死胎的相关因素。方法:回顾分析2016年1月1日至2018年12月31日成都市妇女儿童中心医院收治的116例孕晚期死胎的临床资料,探讨孕晚期死胎的原因。结果:死胎发生率0.33%(207/62574),孕晚期死胎发生率为0.185%(116/62574);胎动减少占65.51%。死胎原因顺位前五位依次为:母体因素(37.07%,43/116)、胎儿因素(21.55%,25/116)、不明原因(12.93%,15/116)、脐带因素(12.07%,14/116);单个高危因素顺位前五位:原因不明(12.93%)、胎儿生长受限(9.48%)、妊娠期糖尿病(7.76%)、羊水过少/妊娠期高血压疾病(6.90%)、脐带扭转(6.03%)。结论:加强孕期监护,及时发现并干预母体因素;重视产前诊断,及时发现胎儿因素;积极开展基因及染色体检查,明确不明原因死胎死因;加强孕妇自我监护,及时寻求帮助及处理,最大可能减少死胎的发生。     

死胎病因及管理

死胎的主要原因包括妊娠前母体疾病,如糖尿病,以及妊娠期并发症,如产前出血、妊娠期肝内胆汁淤积症、胎儿生长受限、单绒毛膜双胎、感染等。脐动脉彩色超声多普勒有助于预测死胎病因。小剂量阿司匹林（60～80 mg）有助于预防高危妊娠孕妇发生子痫前期及其他不良围生期结局。死胎尸检、胎盘病理检查和胎母出血检测等是死胎病因检查的基本手段。     

死胎病史患者再次妊娠的孕期和分娩管理

<正>目前我国对死胎的定义参照了美国国家卫生统计中心的标准[1],即妊娠≥20周或胎儿体质量≥350 g, 胎儿分娩时无呼吸、心跳、脐带搏动或随意肌的明确运动等生命迹象。据估计,有死胎病史的妇女再次发生死胎(即复发性死胎)的风险较前增加了2～10倍[2,3],无疑对孕妇及家庭带来巨大的心理负担和精神压力。因此,对死胎病史患者再次妊娠的孕期和分娩期管理极为重要。孕妇发生复发性死胎的风险具体取决于以下因素:母亲的种族和既往死胎的特征,     

死胎的病因与预防

死胎是妊娠最严重的并发症之一。死胎的病因多样且复杂,但仍有部分死胎原因不明。一般人群筛查包括监测胎动、胎儿生长发育和生化指标。降低死胎风险的措施包括识别高危人群、产前监测和适时分娩。从死胎病因着手发现高危人群、加强监测并及时干预,有可能减少死胎的发生。     

妊娠期肝内胆汁淤积症死胎14例临床分析

目的 :通过 14例妊娠期肝内胆汁淤积症孕妇发生死胎的病例分析 ,探讨死胎发生原因及预防处理措施。方法 :回顾性分析 1995年 1月至 2 0 0 0年 12月我院收治的妊娠期肝内胆汁淤积症死胎病例资料。结果 :14例妊娠期肝内胆汁淤积症死胎均发生于妊娠晚期 ,92 .9%发生于 37周左右 ,且胎死宫内之前无明显胎动减少或胎儿监护异常等征兆 ,但绝大多数孕妇有规律或不规律宫缩。尸检示胎儿在宫内存在急性缺氧。结论 :妊娠期肝内胆汁淤积症死胎常常突然发生 ,难以预测 ,对已确诊的妊娠期肝内胆汁淤积症患者应加强治疗及胎儿监护 ,适时终止妊娠 ,降低围生儿死亡率。     

美国妇产科医师学会“死胎管理专家共识2020版”要点解读

正死胎是最常见的不良妊娠结局之一,其评估和管理一直都是产科临床面临的挑战。死胎的定义普遍采用美国国家卫生统计中心的标准~([1]),即妊娠≥20周或胎儿体重≥350 g,胎儿分娩时无呼吸、心跳、脐带搏动或随意肌的明确运动等生命迹象。由于严重胎儿畸形或不能存活的胎膜早破而引产的情况不属于死胎范畴。目前,我国对死胎的定义也采用上述诊断标准。2020年美国妇产科医师学会(ACOG)发布了死胎管理专家共识(Management of Stillbirth)~([2]),该共识总结并更新了死胎的相关病因和危险因素,重点对死胎的评估和管理提出了15条推荐。     

Prospective risk of stillbirth in multiple-gestation pregnancies: a population-based analysis

OBJECTIVE: To evaluate the prospective risk of stillbirth in multiple gestations. METHODS: We conducted a retrospective analysis of birth notifications and infant mortality records relating to all multiple gestations to residents in a predefined health district. The incidence of live births and stillbirths was used to calculate the prospective risk of stillbirth at each week of gestation. RESULTS: The risk of stillbirth in multiple gestations increased from 1:3333 at 28 weeks' gestation to 1:69 at 39 or more weeks' gestation. The stillbirth risk in multiple gestations at 39 weeks surpassed that of postterm singleton pregnancies (1:526). CONCLUSION: Multiple gestations at 37-38 weeks have a risk of stillbirth equivalent to that of postterm singleton pregnancy. Because multiple gestations rarely proceed beyond 39 weeks, and because stillbirth risk increases several-fold beyond this stage, elective delivery might be justified at this gestational age.     

Investigation and management of stillbirth

Stillbirth describes the delivery of a baby with no signs of life in relation to thresholds of either gestational age or birthweight. In the UK, a stillbirth is legally defined as the delivery of a baby at or after 24 weeks’ gestation or 500 g where gestation is unknown. A history of previous stillbirth remains one of the strongest risk factors for subsequent stillbirth and other adverse outcomes in a subsequent pregnancy. According to World Health Organization (WHO), there are nearly 2 million stillbirths globally every year. There is a drive to reduce the rate of stillbirths by 50% in England by 2025 and a global target of 12 or fewer stillbirths per 1000 total births in every country by 2030. The significant psychological burden placed on parents following a stillbirth and the associated increased risk of complications in subsequent pregnancies need appropriate management. This article covers the investigation and management of stillbirth reflecting current UK practice.     

Totgeburt und plötzlicher Kindstod

During the last 30 years the rate of stillbirths in industrial countries has remained nearly identical, while neonatal mortality und the incidence of the sudden infant death syndrome (SIDS) has declined significantly. This observation is in contrast to the decline of stillbirths due to placental insufficiency, maternal diabetes mellitus, preeclampsia, rhesus incompatibility and fetal aneuploidy. However, the incidence of unexplained stillbirths has increased. The decrease of the incidence of the sudden infant death syndrome proves that prevention of diseases of unknown origin is possible. Smoking, obesity and an excessive increase in body weight before pregnancy are modifiable risk factors for intrauterine stillbirth. The detection and treatment of diabetes mellitus, gestational diabetes and arterial hypertension are effective measures in pregnancy to reduce the risk for stillbirth. The induction of labor at term is also effective in the reduction of stillbirths, however, the burden of elective induction with all of the possible negative effects has to be balanced against the benefit of avoiding intrauterine deaths as approximately 300 labor inductions with the corresponding disadvantages, would be necessary to avoid 1 stillbirth.     

Prolonged pregnancy: evaluating gestation-specific risks of fetal and infant mortality

Objective To evaluate gestation-specific risks of stillbirth, neonatal and post-neonatal mortality.
Design Retrospective analysis of 171,527 notified births (1989–1991) and subsequent infant survival at one year, from community child health records.
Setting Notifications from maternity units in the North East Thames Region, London.
Main outcome measures The incidence of births, stillbirths, neonatal and post-neonatal deaths at each gestation after 28 completed weeks. Mortality rates per 1000 total or live births and per 1000 ongoing pregnancies at each gestation were calculated.
Results The rates of stillbirth at term (2.3 per 1000 total births) and post-term (1.9 per 1000 total births) were similar. When calculated per 1000 ongoing pregnancies, the rate of stillbirth increased six-fold from 0.35 per 1000 ongoing pregnancies at 37 weeks to 2.12 per 1000 ongoing pregnancies at 43 weeks of gestation. Neonatal and post-neonatal mortality rates fell significantly with advancing gestation, from 15 1.4 and 31.7 per 1000 live births at 28 weeks, to reach a nadir at 41 weeks of gestation (0.7 and 1.3 per 1000 live births, respectively), increasing thereafter in prolonged gestation to 1.6 and 2.1 per 1000 live births at 43 weeks of gestation. When calculated per 1000 ongoing pregnancies, the overall risk of pregnancy loss (stillbirth + infant mortality) increased eight-fold from 0.7 per 1000 ongoing pregnancies at 37 weeks to 5.8 per 1000 ongoing pregnancies at 43 weeks of gestation.
Conclusion The risks of prolonged gestation on pregnancy are better reflected by calculating fetal and infant losses per 1000 ongoing pregnancies. There is a significant increase in the risk of stillbirth, neonatal and post-neonatal mortality in prolonged pregnancy. This study provides accurate data on gestation-specific risks of pregnancy loss, enabling pregnant women and their carers to judge the appropriateness of obstetric intervention.     

Maternal medical disease: risk of antepartum fetal death

Although certain maternal medical conditions increase the risk of antepartum fetal death, improvements in medical and obstetric care have decreased the likelihood of stillbirth. This article examines the current stillbirth rates reported in pregnancies complicated by common medical diseases. The reported stillbirth rates are expressed as the number of stillbirths occurring at > or = 20 weeks of gestation per 1,000 births in patients with the condition. Overall, about 10% of all fetal deaths are related to maternal medical illnesses such as hypertension, diabetes, obesity, systemic lupus erythematosus, chronic renal disease, thyroid disorders, and cholestasis of pregnancy. The early recognition of maternal medical diseases provides an opportunity for increased surveillance and interventions that may lead to more favorable pregnancy outcomes.     

Schwangerschaft am Termin

In Germany 75% of the total perinatal mortality is caused by antenatal fetal deaths and 40% of stillbirths occur at or later than 38 weeks of gestation. The rate of stillbirths increases 3 to 4-fold between 37 and 42 weeks of gestation relative to ongoing pregnancies. Mothers with advanced maternal age and primiparae are at higher risk of stillbirth. Neonatal complications show a continuous increase between 37 and 42 weeks of gestation. Pregnancy beyond 40 weeks is associated with significant risks to the pregnant women such as increased rate of cesarean delivery, operative vaginal delivery, postpartum hemorrhage, endomyometritis and birth injuries. At a gestational age of 41 weeks and accurate pregnancy dating, induction of labor is recommended without causing an increase in the frequency of cesarean deliveries. If additional risks for placental insufficiency are present, delivery from 37 weeks onwards might improve maternal and fetal outcome.     

Incidence of stillbirth and perinatal mortality and their associated factors among women delivering at Harare Maternity Hospital, Zimbabwe: a cross-sectional retrospective analysis

BACKGROUND: Death of an infant in utero or at birth has always been a devastating experience for the mother and of concern in clinical practice. Infant mortality remains a challenge in the care of pregnant women worldwide, but particularly for developing countries and the need to understand contributory factors is crucial for addressing appropriate perinatal health. METHODS: Using information available in obstetric records for all deliveries (17,072 births) at Harare Maternity Hospital, Zimbabwe, we conducted a cross-sectional retrospective analysis of a one-year data, (1997-1998) to assess demographic and obstetric risk factors for stillbirth and early neonatal death. We estimated risk of stillbirth and early neonatal death for each potential risk factor. RESULTS: The annual frequency of stillbirth was 56 per 1,000 total births. Women delivering stillbirths and early neonatal deaths were less likely to receive prenatal care (adjusted relative risk [RR] = 2.54; 95% confidence intervals [CI] 2.19-2.94 and RR = 2.52; 95% CI 1.63-3.91), which for combined stillbirths and early neonatal deaths increased with increasing gestational age (Hazard Ratio [HR] = 3.98, HR = 7.49 at 28 and 40 weeks of gestation, respectively). Rural residence was associated with risk of infant dying in utero, (RR = 1.33; 95% CI 1.12-1.59), and the risk of death increased with increasing gestational age (HR = 1.04, HR = 1.69, at 28 and 40 weeks of gestation, respectively). Older maternal age was associated with risk of death (HR = 1.50; 95% CI 1.21-1.84). Stillbirths were less likely to be delivered by Cesarean section (RR = 0.64; 95% CI 0.51-0.79), but more likely to be delivered as breech (RR = 4.65; 95% CI 3.88-5.57, as were early neonatal deaths (RR = 3.38; 95% CI 1.64-6.96). CONCLUSION: The frequency of stillbirth, especially macerated, is high, 27 per 1000 total births. Early prenatal care could help reduce perinatal death linking the woman to the health care system, increasing the probability that she would seek timely emergency care that would reduce the likelihood of death of her infant in utero. Improved quality of obstetric care during labor and delivery may help reduce the number of fresh stillbirths and early neonatal deaths.     

First-trimester metabolomic prediction of stillbirth

Background: Stillbirth remains a major problem in both developing and developed countries. Omics evaluation of stillbirth has been highlighted as a top research priority.

Objective: To identify new putative first-trimester biomarkers in maternal serum for stillbirth prediction using metabolomics-based approach.

Methods: Targeted, nuclear magnetic resonance (NMR) and mass spectrometry (MS), and untargeted liquid chromatography-MS (LC-MS) metabolomic analyses were performed on first-trimester maternal serum obtained from 60 cases that subsequently had a stillbirth and 120 matched controls. Metabolites by themselves or in combination with clinical factors were used to develop logistic regression models for stillbirth prediction. Prediction of stillbirths overall, early (<28 weeks and <32 weeks), those related to growth restriction/placental disorder, and unexplained stillbirths were evaluated.

Results: Targeted metabolites including glycine, acetic acid, L-carnitine, creatine, lysoPCaC18:1, PCaeC34:3, and PCaeC44:4 predicted stillbirth overall with an area under the curve [AUC, 95% confidence interval (CI)]?=?0.707 (0.628–0.785). When combined with clinical predictors the AUC value increased to 0.740 (0.667–0.812). First-trimester targeted metabolites also significantly predicted early, unexplained, and placental-related stillbirths. Untargeted LC-MS features combined with other clinical predictors achieved an AUC (95%CI)?=?0.860 (0.793–0.927) for the prediction of stillbirths overall. We found novel preliminary evidence that, verruculotoxin, a toxin produced by common household molds, might be linked to stillbirth.

Conclusions: We have identified novel biomarkers for stillbirth using metabolomics and demonstrated the feasibility of first-trimester prediction.     

Reducing stillbirths: screening and monitoring during pregnancy and labour

Background

Screening and monitoring in pregnancy are strategies used by healthcare providers to identify high-risk pregnancies so that they can provide more targeted and appropriate treatment and follow-up care, and to monitor fetal well-being in both low- and high-risk pregnancies. The use of many of these techniques is controversial and their ability to detect fetal compromise often unknown. Theoretically, appropriate management of maternal and fetal risk factors and complications that are detected in pregnancy and labour could prevent a large proportion of the world's 3.2 million estimated annual stillbirths, as well as minimise maternal and neonatal morbidity and mortality.

Methods

The fourth in a series of papers assessing the evidence base for prevention of stillbirths, this paper reviews available published evidence for the impact of 14 screening and monitoring interventions in pregnancy on stillbirth, including identification and management of high-risk pregnancies, advanced monitoring techniques, and monitoring of labour. Using broad and specific strategies to search PubMed and the Cochrane Library, we identified 221 relevant reviews and studies testing screening and monitoring interventions during the antenatal and intrapartum periods and reporting stillbirth or perinatal mortality as an outcome.

Results

We found a dearth of rigorous evidence of direct impact of any of these screening procedures and interventions on stillbirth incidence. Observational studies testing some interventions, including fetal movement monitoring and Doppler monitoring, showed some evidence of impact on stillbirths in selected high-risk populations, but require larger rigourous trials to confirm impact. Other interventions, such as amniotic fluid assessment for oligohydramnios, appear predictive of stillbirth risk, but studies are lacking which assess the impact on perinatal mortality of subsequent intervention based on test findings. Few rigorous studies of cardiotocography have reported stillbirth outcomes, but steep declines in stillbirth rates have been observed in high-income settings such as the U.S., where cardiotocography is used in conjunction with Caesarean section for fetal distress.

Conclusion

There are numerous research gaps and large, adequately controlled trials are still needed for most of the interventions we considered. The impact of monitoring interventions on stillbirth relies on use of effective and timely intervention should problems be detected. Numerous studies indicated that positive tests were associated with increased perinatal mortality, but while some tests had good sensitivity in detecting distress, false-positive rates were high for most tests, and questions remain about optimal timing, frequency, and implications of testing. Few studies included assessments of impact of subsequent intervention needed before recommending particular monitoring strategies as a means to decrease stillbirth incidence. In high-income countries such as the US, observational evidence suggests that widespread use of cardiotocography with Caesarean section for fetal distress has led to significant declines in stillbirth rates. Efforts to increase availability of Caesarean section in low-/middle-income countries should be coupled with intrapartum monitoring technologies where resources and provider skills permit.