Prediction and prevention of recurrent stillbirth

Stillbirth is one of the most common adverse pregnancy outcomes in the United States, occurring in one out of every 200 pregnancies. There is a paucity of information on the outcome of pregnancies after stillbirth. Prior stillbirth is associated with a twofold to 10-fold increased risk of stillbirth in the future pregnancy. The risk depends on the etiology of the prior stillbirth, presence of fetal growth restriction, gestational age of the prior stillbirth, and race. Categorization of the cause of the initial stillbirth will allow better estimates of individual recurrence risk and guide management. A history of stillbirth also increases the risk of other adverse pregnancy outcomes in the subsequent pregnancy such as placental abruption, cesarean delivery, preterm delivery, and low birth weight infants. Prospective studies have revealed an increased risk of stillbirth with low pregnancy-associated plasma protein A, elevated maternal serum alpha fetoprotein, abnormal uterine artery Doppler studies, and antiphospholipid antibodies. However, the positive predictive value of these factors individually is poor. Because fetal growth restriction is associated with almost half of all stillbirths, the correct diagnosis of fetal growth restriction is essential. The use of individualized or customized growth standards will improve prediction of adverse pregnancy outcome by distinguishing growth-restricted fetuses from constitutionally small, healthy fetuses. Antepartum fetal surveillance and fetal movement counting are also mainstays of poststillbirth pregnancy management.     

Stillbirth Following Normal Ultrasound Findings and Maternal Placental Growth Factor Levels

BackgroundAttempts to reduce the current rate of antepartum stillbirth in the late third trimester have largely focused on the accurate identification of fetal growth restriction. Universal ultrasound significantly increases detection, especially when combined with maternal angiogenic growth factors, but this screening strategy is not well suited to identify umbilical cord pathology. While this poses unique challenges to pregnancy care, the recurrence risk of cord obstruction is low in comparison with many intrinsic placental diseases.CaseA 30-year-old woman with normal uterine artery Doppler waveforms, fetal growth ultrasounds, and circulating placental growth factor experienced an unexpected third-trimester stillbirth. Placental pathology demonstrated fetal vascular malperfusion and cord hyper-coiling.ConclusionDespite normal placental function, the otherwise healthy fetus is at risk of antepartum stillbirth due to cord-related pathology.     

Maternal uterine artery Doppler flow velocimetry and the risk of stillbirth

OBJECTIVE: We sought to relate the risk of antepartum stillbirth to uterine artery Doppler flow velocimetry at 22-24 weeks. METHODS: Data were available from 30,519 unselected women from seven units in the UK who had uterine artery Doppler performed between 22 and 24 weeks of gestation. The risk of stillbirth (n=109) was assessed using time to event and logistic regression analysis. Stillbirths were subdivided into placental (due to abruption, preeclampsia, or growth restriction) or unexplained. RESULTS: The risk of placental stillbirth was increased among women with a mean pulsatility index in the top decile (adjusted hazard ratio [HR] 5.5, 95% confidence interval [CI] 2.8-10.6) and those with a bilateral notch (adjusted HR 3.9, 95% CI 2.0-7.8). The relationship between a mean pulsatility index in the top decile and the risk of unexplained stillbirth was weaker (adjusted HR 2.5, 95% CI 1.1-5.6) and there was no association with a bilateral notch. Placental stillbirths occurred at earlier gestations than unexplained stillbirths (median [interquartile range] 30 [26-36] compared with 38 [36-40], P<.001). Consequently, being in the top 5% of predicted risk of stillbirth on the basis of the combination of mean pulsatility index and notching was a good predictor (sensitivity, specificity, and positive likelihood ratio) of all cause stillbirth up to 32 weeks (58%, 95%, and 12.1, respectively) but a poor predictor of stillbirth at later gestations (7%, 95%, and 1.3, respectively). CONCLUSION: Abnormal uterine artery Doppler was a better predictor of the risk of stillbirth due to placental causes than unexplained stillbirth. Consequently, abnormal uterine artery Doppler was a good predictor of stillbirth at extreme preterm gestations but a poor predictor of stillbirth at term. LEVEL OF EVIDENCE: II.     

The risk of unexplained antepartum stillbirth in second pregnancies following caesarean section in the first pregnancy

Objective  To determine if a previous caesarean section increases the risk of unexplained antepartum stillbirth in second pregnancies.
Study design  Retrospective cohort study.
Setting  Large Canadian perinatal database.
Population  158 502 second births.
Methods  Data were obtained from a large perinatal database, which supplied data on demographics, pregnancy complications, maternal medical conditions, previous caesarean section and pregnancy outcomes.
Main outcome measures  Total and unexplained stillbirth.
Results  The antepartum stillbirth rate was 3.0/1000 in the previous caesarean section group compared with 2.7/1000 in the previous vaginal delivery group ( P = 0.46). Multivariate logistic regression modelling, including terms for maternal age (polynomial), weight >91 kg, smoking during pregnancy, pre-pregnancy hypertension and diabetes, did not document an association between previous caesarean section and unexplained antepartum stillbirth (OR 1.27, 95% CI 0.92–1.77).
Conclusion  Caesarean section in the first birth does not increase the risk of unexplained antepartum stillbirth in second pregnancies.     

Adverse maternal and fetal outcomes and deaths related to preeclampsia and eclampsia in Haiti

ObjectiveThe purpose of this study was to define the prevalence and clinical characteristics of preeclampsia and eclampsia at a hospital in rural Haiti.MethodsThis is a retrospective review of women presenting to Hôpital Albert Schweitzer (HAS) in Deschapelles, Haiti with singleton pregnancy and diagnosis of preeclampsia or eclampsia from January 1, 2011 through December 31, 2012. Hospital charts were reviewed to obtain medical and prenatal history, hospital course, delivery information, and fetal/neonatal outcomes. The outcomes included placental abruption, antepartum eclampsia, postpartum eclampsia, maternal death, birthweight <2500 g and stillbirth. Data are presented as median (quartile 1, quartile 3) or n (%) and risk ratios.ResultsDuring the study period, 1743 women were admitted to the maternity service at HAS and 290 (16.6%) were diagnosed with preeclampsia or eclampsia. Only singleton pregnancies were analyzed (N = 270). Nearly all (95.0%) patients admitted with preeclampsia had severe preeclampsia. There were 83 patients with eclampsia (30.7%) of which 61 (73.4%) had antepartum eclampsia. There were 48 stillbirths (17.8%) and 5 maternal deaths (1.9%). Patients with antepartum eclampsia were younger, more likely to be nulliparous and had less prenatal care compared to women with antepartum preeclampsia. Antepartum eclampsia was associated with placental abruption and maternal death.ConclusionsThe rates of preeclampsia and its associated complications, such as eclampsia, placental abruption, maternal death and stillbirth, are high at this facility in Haiti. Such data are essential to developing region-specific systems to prevent preeclampsia-related complications.     

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。     

Factor V Leiden mutation: the most commonly inherited risk factor for venous thromboembolism

Factor V Leiden mutation is a common genetic risk factor for venous thrombosis. It has been documented in up to 65% of patients with unexplained venous thromboembolism. This genetic mutation is now known to be the most common inherited cause of activated protein C (APC) resistance. Recently, FV Leiden mutation has been associated with adverse pregnancy outcomes (including recurrent fetal loss, severe preeclampsia, placental abruption, intrauterine growth restriction and stillbirth), in addition to venous thromboembolic disorders. In this article, we discuss the genetic basis, diagnosis and clinical significance of FV Leiden mutation. Awareness of the clinical manifestations associated with FV Leiden mutation should ensure screening of appropriate populations and prophylaxis against thromboembolic disease when indicated.     

Antepartum testing in patients with hypertensive disorders in pregnancy

Antepartum fetal testing in pregnant patients with hypertensive disorders may be beneficial in preventing stillbirth and hypoxic sequelae in the fetus. The highest risk patients in this category are those with intrauterine growth restriction, superimposed preeclampsia, associated medical complications such as diabetes, systemic lupus erythematosis, chronic renal disease, or history of a prior stillbirth. The current recommended method of primary testing is a twice weekly modified biophysical profile with either a full BPP or a contraction stress test for backup evaluation of those patients with lack of reactivity or decreased amniotic fluid volume on a modified biophysical profile. Even uncomplicated patients with chronic hypertension or pregnancy-induced hypertension carry an increased risk of perinatal mortality and for these patients testing should begin at 33 to 34 weeks gestation. Patients with complications of intrauterine growth restriction, preeclampsia, diabetes, systemic lupus erythematosis, or chronic renal disease should have antepartum testing begin when intervention for fetal indications is judged to be appropriate, usually beginning at about 26 weeks gestation. Doppler velocimetry may be helpful in further evaluation of those patients in the early third trimester with abnormal primary testing.     

Characteristics of antepartum and intrapartum eclampsia in the National Maternal and Child Health Center in Cambodia

AIM: To measure maternal and perinatal outcome and analyze risk factors for antepartum and intrapartum eclampsia, which is one of main causes of high maternal mortality at the top referral hospital in the Kingdom of Cambodia. METHODS: A hospital-based retrospective study of 164 antepartum and intrapartum eclampsia cases out of 20,449 deliveries. RESULTS: Overall case-fatality rate was 12%. Rate of stillbirth and low birth weight were 20% and 44%, respectively. Eighty percent of the cases presented signs of severe pre-eclampsia and 27% of the patients who gave birth received cesarean section. Living outside the capital city, teenage pregnancy and twin pregnancy are more frequently associated with eclampsia. CONCLUSION: Antepartum and intrapartum eclampsia is associated with severe pre-eclampsia and with poor maternal and perinatal outcome. Recommendations to reduce the burden of eclampsia are promoting and improving quality of antenatal care and health education especially in the third trimester; increasing access to high-quality essential obstetric care; improving the service delivery in rural areas; and monitoring the progress by hospital data.     

Maternal weight, pregnancy weight gain, and the risk of antepartum stillbirth

OBJECTIVE: This study investigated whether the risk of antepartum stillbirth increases with body mass index during early pregnancy and also investigated the association between weight gain during pregnancy and the risk of antepartum stillbirth.Study Design: This population-based case-control study included 649 women with antepartum stillbirths and 690 control subjects among Swedish nulliparous women. RESULTS: Compared with lean mothers (body mass index < or = 19.9 kg/m2), the odds ratios for risk of antepartum deaths were as follows: normal weight (body mass index, 20.0-24.9 kg/m2) odds ratio, 1.2 (95% confidence interval, 0.8-1.7); overweight (body mass index 25.0-29.9 kg/m2), odds ratio, 1.9 (95% confidence interval, 1.2-2.9); and obese (body mass index > or = 30.0 kg/m2) odds ratio, 2.1 (95% confidence interval, 1.2-3.6). For term antepartum death corresponding risks were even higher, with odds ratios of 1.6 (95% confidence interval, 0.9-2.6) for normal weight, 2.7 (95% confidence interval, 1.5-5.0) for overweight, and 2.8 (95% confidence interval, 1.3-6.0) for obese women, respectively. Maternal weight gain during pregnancy was not associated with risk of antepartum stillbirth. CONCLUSION: Maternal overweight condition increased the risk of antepartum stillbirth, especially term antepartum stillbirth, whereas weight gain during pregnancy was not associated with risk.     

死胎的预测及其高危人群的管理

死胎是各种高危因素下母体、胎儿、胎盘疾病的终末期结局。早中孕期联合母体病史、超声胎儿生长及子宫动脉多普勒血流评估、母体血清胎盘生长因子,对胎盘受损所致死胎的预测价值较高,但对足月死胎的预测价值有限。正确识别死胎的高危因素,加强高危人群的孕前及孕期管理,有效利用各种产前监护手段以及适时分娩,可降低死胎的发生率。     

Restricted fetal growth in sudden intrauterine unexplained death

BACKGROUND: Unexplained antepartum stillbirth is a common cause of perinatal death, and identifying the fetus at risk is a challenge for obstetric practice. Intrauterine growth restriction (IUGR) is associated with a variety of adverse perinatal outcomes, but reports on its impact on unexplained stillbirths by population-based birthweight standards have been varying, including both unexplained and unexplored stillbirths. AIM: We have studied IUGR, assessed by individually adjusted fetal weight standards, in antepartum deaths that remained unexplained despite thorough postmortem investigations. METHODS: Antenatal health cards from a complete population-based 10-year material of 76 validated sudden intrauterine unexplained deaths were compared to those of 582 randomly selected liveborn controls. Birthweight <10th percentile of the individualized standard adjusted for gestational age, maternal height, weight, parity, ethnicity, and fetal gender was defined as growth restriction. RESULTS: 52% of unexplained stillbirths were growth restricted, with a mean gestational age at death of 35.1 weeks. Suboptimal growth was the most important fetal determinant for sudden intrauterine unexplained death (odds ratio 7.0, 95% confidence interval 3.3-15.1). Concurrent maternal overweight or obesity, high age, and low education further increase the risk. Overweight and obesity increase the risk irrespective of fetal growth, and while high maternal age increases the risk of the normal weight fetus, it is not associated to growth restriction as a precursor of sudden intrauterine unexplained death. CONCLUSIONS: IUGR is an important risk factor of sudden intrauterine unexplained death, and this should be excluded in pregnancies with any other risk factor for sudden intrauterine unexplained death.     

Doppler investigation of uteroplacental blood flow resistance in the second trimester: a screening study for pre-eclampsia and intrauterine growth retardation

OBJECTIVE--To assess the screening properties of a mid-trimester uteroplacental Doppler scan in a normal unselected population. DESIGN--A cross-sectional study measuring an averaged resistance index (AVRI) from four sites (left and right uterine and arcuate arteries) with continuous wave Doppler ultrasound. SETTING--Routine booking ultrasound, King's College Hospital, London. SUBJECTS--977 women at 16-24 weeks gestation. MAIN OUTCOME MEASURES--Intrauterine death, birthweight, pregnancy-induced hypertension (PIH), antepartum haemorrhage. RESULTS--There was a 96.5% follow-up. Pregnancies with high AVRI values had a higher prevalence of proteinuric hypertension, placental abruption, small-for-gestational-age babies, and fetal loss. When AVRI was greater than 95th centile, the overall risk of pregnancy complications was 67%, and the risk of a severe complication was 25%. However, the sensitivity of the test for these complications was only 13% and 21% respectively. The risk for an individual woman with a high AVRI of developing a complication was increased by up to 9.8 times. CONCLUSION--Although Doppler screening does detect a unifying defect leading to perinatal death, pre-eclampsia, growth retardation and placental abruption, the predictive values do not yet justify its introduction as a routine test.     

Stillbirth: a review.

Stillbirth occurs in nearly 1% of all births in the USA, and is one of the most common but least studied adverse pregnancy outcomes. The many risk factors for and causes of stillbirth are presented. Over the past several decades, the rate of stillbirth has been substantially reduced, with the reduction most apparent in those stillbirths previously occurring at term and/or in labor. Reductions have occurred because of reductions in risk factors (i.e. prevention of Rh disease and better control of diabetes), better antepartum monitoring of those with risk factors followed by early delivery for those fetuses found to be at risk (i.e. growth restriction, maternal pre-eclampsia), better intrapartum fetal monitoring, increases in Cesarean section for those at risk, and early detection of congenital anomalies followed by termination prior to the time that these early fetal deaths are classified as stillbirths. Finally, the value of using fetal autopsy and placental examination to determine the cause of death accurately, both for research purposes and for patient counseling in future pregnancies, is explored.     

Comprehensive Review of the Stillborn Placenta

Stillbirth is a common complication of pregnancy, affecting one in every 160 women in the United States who are pregnant. Stillbirth has a significant adverse medical and psychological impact on families. Identifying the cause of stillbirth can yield recommendations for the management of future pregnancies, provide a risk of recurrence, and give families a sense of closure. The placental examination is one component of a comprehensive stillbirth investigation. A systematic approach to the examination of the placenta is presented, along with an explanation of critical findings that have been associated with stillbirth. A checklist for placental evaluation by the provider who attends the birth is provided, along with information on stillbirth assessment programs.     

Risk factors for sudden intrauterine unexplained death: epidemiologic characteristics of singleton cases in Oslo, Norway, 1986-1995

OBJECTIVE: The epidemiologic characteristics of unexplained stillbirths are largely unknown or unreliable. We define sudden intrauterine unexplained death as a death that occurs antepartum and results in a stillbirth for which there is no explanation despite postmortem examinations, and we present risk factors for this type of stillbirth in singleton gestations.Study Design: Singleton antepartum stillbirths (n = 291) and live births (n = 582) in Oslo were included and compared with national data (n = 2025 and n = 575,572, respectively). Explained stillbirths (n = 165) and live births in Oslo served as controls for the cases of sudden intrauterine unexplained death (n = 76) in multiple logistic regression analyses. RESULTS: One fourth of stillbirths remain unexplained. The risk of sudden intrauterine unexplained death (1/1000) increased with gestational age, high maternal age, high cigarette use, low education, and overweight or obesity. Primiparity and previous stillbirths or spontaneous abortions were not associated with sudden intrauterine unexplained death. CONCLUSIONS: Risk factors for sudden intrauterine unexplained death are identifiable by basic antenatal care. Adding unexplored stillbirths to the unexplained ones conceals several risk factors and underlines the necessity of a definition that includes thorough postmortem examinations.     

Adverse pregnancy outcomes are associated with multiple maternal thrombophilic factors

OBJECTIVE: To determine to what extent adverse pregnancy outcomes are associated with thrombophilia. STUDY DESIGN: We studied 31 women who had HELLP syndrome, placental abruption, fetal growth restriction or unexplained stillbirth (study group), matched with 12 controls. All women were tested for: Factor V, Prothrombin, methylenetetrahydrofolate reductase gene (MTHFR) mutations; for Protein C, S and Antithrombin III deficiency; for lupus anticoagulant. Correlation with 24h BP monitoring and uterine Doppler velocimetry indexes at 22-24 weeks' gestation was performed. RESULTS: Women with multiple thrombophilic factors had a significant lower birth weight (1568.33+/-146.8 g versus 2546.45+/-438 g), higher 24 h mean diastolic blood pressure at second trimester (76.3+/-12.5 mmHg versus 65.2+/-7.8 mmHg) and higher RI of uterine arteries (0.69+/-0.05 versus 0.50+/-0.15) than women with single thrombophilic factor. CONCLUSION: Multiple thrombophilic factors carry a major additional risk for adverse maternal and fetal outcomes and correlate well with placental maladaptation as indicated by uterine Doppler velocimetry and 24h BP monitoring.     

血栓性疾病史女性孕前系统管理

既往血栓性疾病史是妊娠女性发生静脉栓塞的首要高危因素,其造成的肺栓塞是危及孕妇生命的主要原因,同时血栓性疾病史孕妇也是子痫前期、死胎、胎盘早剥等不良妊娠并发症的高危人群。对这些人群进行系统孕前管理是减少或杜绝此类恶性事件发生的关键。     

Uteroplacental blood flow velocity-time waveforms in normal and complicated pregnancy

Summary. A simple continuous wave Doppler ultrasound system for recording arterial flow velocity waveforms in branches of the uterine artery in the placental bed is described. Twelve normal pregnancies were studied serially from 20 weeks to delivery. The diastolic flow velocity expressed as a percentage of the systolic provides an index of downstream vascular bed resistance and perfusion. This always exceeded 50% in normal pregnancy and there was a small increase with gestational age indicative of a decreasing flow resistance. Of the 91 complicated pregnancies, studied because of potential uteroplacental insufficiency and fetal risk, 25 resulted in the birth of an infant small-for-gestational-age. In 15 the uterine artery flow velocity waveform revealed a pattern of low diastolic flow velocity. It is postulated that these represent a subgroup of growth-retarded fetuses in whom there is reduced uterine artery perfusion. Reduced uterine artery diastolic flow velocity in these patients was associated with reduced umbilical artery diastolic flow velocity on the fetal side of the placenta. In contrast the 10 small-for-gestation infants associated with normal uterine artery waveforms suggest a primary fetal cause. Twelve patients with severe hypertensive disease of pregnancy were studied. Nine were associated with reduced uterine artery diastolic flow velocity (reduced uterine artery perfusion) consistent with vasospasm in the branches of the uterine artery in the placental bed.     

Uteroplacental blood flow velocity-time waveforms in normal and complicated pregnancy

A simple continuous wave Doppler ultrasound system for recording arterial flow velocity waveforms in branches of the uterine artery in the placental bed is described. Twelve normal pregnancies were studied serially from 20 weeks to delivery. The diastolic flow velocity expressed as a percentage of the systolic provides an index of downstream vascular bed resistance and perfusion. This always exceeded 50% in normal pregnancy and there was a small increase with gestational age indicative of a decreasing flow resistance. Of the 91 complicated pregnancies, studied because of potential uteroplacental insufficiency and fetal risk, 25 resulted in the birth of an infant small-for-gestational-age. In 15 the uterine artery flow velocity waveform revealed a pattern of low diastolic flow velocity. It is postulated that these represent a subgroup of growth-retarded fetuses in whom there is reduced uterine artery perfusion. Reduced uterine artery diastolic flow velocity in these patients was associated with reduced umbilical artery diastolic flow velocity on the fetal side of the placenta. In contrast the 10 small-for-gestation infants associated with normal uterine artery waveforms suggest a primary fetal cause. Twelve patients with severe hypertensive disease of pregnancy were studied. Nine were associated with reduced uterine artery diastolic flow velocity (reduced uterine artery perfusion) consistent with vasospasm in the branches of the uterine artery in the placental bed.