Prepregnancy obesity and fetal death: a study within the Danish National Birth Cohort

OBJECTIVE: To examine the association between high prepregnancy body mass index and fetal death, allowing for the effects of gestational age, weight gain, and maternal diseases in pregnancy. METHODS: Prepregnancy body mass index (BMI) and fetal death were examined in the Danish National Birth Cohort among 54,505 pregnant women who participated in a comprehensive interview during the second trimester. Pregnancy outcomes were obtained from registers and medical records. Cox regression analyses with delayed entry and time-dependent covariates were used to estimate the risk of fetal death. RESULTS: Compared with normal-weight women (18.5 < or = BMI < 25), the risks of fetal death among obese women (BMI > or = 30), expressed as adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were as follows: before week 14: 0.8 (0.5-1.4), weeks 14-19: 1.6 (1.0-2.5), weeks 20-27: 1.9 (1.1-3.3), weeks 28-36: 2.1 (1.0-4.4), weeks 37-39: 3.5 (1.9-6.4), and weeks 40+: 4.6 (1.6-13.4). Overweight women (25 < or = BMI < 30) also experienced a higher risk after 28 weeks, and especially after 40 weeks of gestation (HR 2.9, 95% CI 1.1-7.7). Analysis of stillbirth (fetal death at 28+ completed weeks of gestation) indicated that the effects were not due to obesity-related diseases in pregnancy, nor was weight gain associated with stillbirth. The increased risk of stillbirth among overweight and obese women was partly attributable to inadequate placental function (crude odds ratios 2.1, 95% CI 1.0-4.4, and 5.2, 95% CI 2.5-10.9, respectively). CONCLUSION: Prepregnancy obesity was associated with an increasing excess risk of fetal death with advancing gestation, and placental dysfunction may be a possible contributing factor.     

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.     

Diabetic-associated stillbirth: incidence, pathophysiology, and prevention

All forms of diabetes during pregnancy are associated with an increased risk for stillbirth, defined as fetal death at greater than 20 weeks. The incidence of stillbirth in women who have diabetes has decreased dramatically with improved diabetes care. Diabetic-associated stillbirth is associated with hyperglycemia, resulting in fetal anaerobic metabolism with hypoxia and acidosis. Prevention of stillbirth in women who have diabetes hinges on intensive multidisciplinary prenatal care with control of blood sugars and appropriate fetal surveillance.     

Diabetic-associated stillbirth: incidence, pathophysiology, and prevention

All forms of diabetes during pregnancy are associated with an increased risk for stillbirth, defined as fetal death at greater than 20 weeks. The incidence of stillbirth in women who have diabetes has decreased dramatically with improved diabetes care. Diabetic-associated stillbirth is associated with hyperglycemia, resulting in fetal anaerobic metabolism with hypoxia and acidosis. Prevention of stillbirth in women who have diabetes hinges on intensive multidisciplinary prenatal care with control of blood sugars and appropriate fetal surveillance.     

Advanced maternal age

The average age of women at childbirth in industrialised nations has been increasing steadily for approximately 30 years. Women aged 35 years or over have an increased risk of gestational hypertensive disease, gestational diabetes, placenta praevia, placental abruption, perinatal death, preterm labour, fetal macrosomia and fetal growth restriction. Unsurprisingly, rates of obstetric intervention are higher among older women. Of particular concern is the increased risk of antepartum stillbirth at term in women of advanced maternal age. In all maternal age groups, the risk of stillbirth is higher among nulliparous women than among multiparous women. Women of advanced maternal age (>40 years) should be given low dose aspirin (in the presence of an additional risk factor for pre-eclampsia) and offered serial ultrasounds for fetal growth and wellbeing; given the increased risk of antepartum stillbirth, induction of labour from 39 weeks’ gestation should be discussed with the woman.     

The analysis of factors predicting antepartum stillbirth

Antepartum stillbirth is the single most common cause of perinatal death. Antepartum stillbirth is associated with fetal abnormality, congenital infection, rhesus isoimmunisation, maternal medical conditions, and complications of pregnancy, such as pre-eclampsia and placental abruption. However, the majority have no direct obstetric cause and are referred to as unexplained. Many of these so-called unexplained deaths are associated with growth restriction. Maternal characteristics, such as age and smoking, are associated with an increased risk of antepartum stillbirth. The risk of stillbirth in late pregnancy is related to the function of the placenta in early pregnancy. Placental function can be assessed using circulating markers in the mothers blood, such as pregnancy associated plasma protein A and alpha-fetoprotein. Invasion of the trophoblast into the uterine vessels is associated with decreased resistance to flow in the uterus and impaired placentation is reflected in high resistance Doppler flow velocity waveforms in the utero-placental circulation. Both circulating placental markers and Doppler indices of resistance to flow are predictive of the risk of antepartum stillbirth. However, none of these tools has sufficient positive predictive value to justify population based screening. Future research in unexplained stillbirth should be directed towards developing better predictive tests to identify women at high risk and the evaluation of interventions in large scale trials.     

Conditions associated with placental dysfunction

Placental dysfunction is a term to describe suboptimal placental function leading to variations in the fetal supply of all its necessary required nutrients as well as the disruption in the cleansing of fetal catabolic products. The dysfunctional placenta may interrupt the manufacturing of other essential factors involved in pregnancy conservation, can compromise the fetal appropriate, atraumatic and sterile medium to grow, the immunologic shield from maternal antibodies and the normal amniotic fluid levels. Placental dysfunction can lead to a group of disorders representing a diverse and important category of pathological processes conducting to fetal and neonatal morbidity and mortality. The mechanisms by which these inflammatory processes cause death and disability are diverse and can be separated into four distinct classes: first, placental damage with loss of function; second, induction of premature labor; third, release of inflammatory mediators; fourth, transplacental infection. Several conditions have been associated with placental dysfunction: IUGR, hypertension, hypoxic-ischemic injury, preterm labor, and fetal death.     

Management of pregnancy complications in women of advanced maternal age

The average age of women at childbirth in high resource obstetric settings has been increasing steadily for approximately 30 years. Women aged 35 years or over have an increased risk of gestational hypertensive disease, gestational diabetes, placenta praevia, placental abruption, perinatal death, preterm labour, fetal macrosomia and fetal growth restriction. Unsurprisingly, rates of obstetric intervention are higher among older women. Of particular concern is the increased risk of antepartum stillbirth at term in women of advanced maternal age. In all maternal age groups, the risk of stillbirth is higher among nulliparous women than among multiparous women. Women of advanced maternal age (>40 years) should be given low dose aspirin in the presence of an additional risk factor for pre-eclampsia and offered serial ultrasounds for fetal growth and wellbeing. Given the increased risk of antepartum stillbirth, induction of labour from 39 weeks’ gestation should be discussed with woman.     

Stillbirth and neonatal outcomes in South Australia, 1991-2000

OBJECTIVES: The purpose of this study was to determine the effect of maternal factors associated with impaired placental function on stillbirth and neonatal death rates in South Australia. STUDY DESIGN: From 1991 to 2000, the South Australian Pregnancy Outcome Unit's population database was searched to identify stillbirths and neonatal deaths in women with maternal medical conditions during pregnancy and in twin and singleton pregnancies. RESULTS: Women with hypertension and carbohydrate intolerance and who smoked during pregnancy had an increased risk of stillbirth. Women with twin pregnancies had a significantly higher stillbirth rate than for singletons at each week of gestational age. An increase in stillbirth rate at later gestations was seen with singletons, with a similar trend in twins but rising from 36 weeks' gestation. CONCLUSION: There is a clinical correlation between maternal factors associated with impaired placental function and increased risk of stillbirth, suggesting that intrauterine fetal death represents the mortality end point in a spectrum of intrauterine hypoxia.     

Poor obstetric outcome in subsequent pregnancies in women with prior fetal death

OBJECTIVE: Patients with recurrent first-trimester spontaneous abortion have been the subject of intensive investigation. However, relatively little is known about second- and third-trimester pregnancy loss. Thus, it is difficult for clinicians to optimally counsel, evaluate, and manage women with previous unexplained fetal death. Our objective was to ascertain the outcome of subsequent pregnancies in patients with prior fetal death. METHODS: Subjects were identified from patients referred for evaluation of fetal death (occurring at >/= 10 weeks of gestation) and having at least one subsequent pregnancy. Patients with antiphospholipid antibodies were excluded. Logistic regression analysis was performed to determine the association of clinical variables with pregnancy outcome. RESULTS: Two hundred thirty subjects met inclusion criteria. Up through the time of their first fetal death, these women had a total of 721 pregnancies, resulting in 268 (37%) live births, 230 (32%) fetal deaths, and 200 (28%) spontaneous abortions. In total, these women had 839 subsequent pregnancies, resulting in 202 (24%) live births, 209 (25%) fetal deaths, and 372 (44%) spontaneous abortions. Univariate logistic regression analysis identified older age at pregnancy (P =.009, odds ratio 0.63, 95% confidence interval 0.42-1.03) and treatment with low-dose aspirin (P =.001, odds ratio 0.41, 95% confidence interval 0.25-0.68) to be associated with a decreased risk for subsequent pregnancy loss. CONCLUSION: Women with prior fetal death are at high risk for subsequent pregnancy loss and recurrent fetal death, with fewer than 25% of pregnancies resulting in surviving infants. These data underscore the need for additional research into the pathophysiology and prevention of recurrent fetal death.     

Défaut de maturation placentaire: une pathologie placentaire de diagnostic anatomopathologique

Some parenchymal placental pathologies are only diagnosed by placental examination. Among these, maturation defect in terminal villi is an infrequent but underdiagnosed placental pathology of the late third trimester. In normalterm placentae, there are several syncytiocapillary membranes in each terminal chorionic villus. Maturation defect is defined by the paucity of the capillaries in terminal chorionic villi and by their abnormal residual central location after 35 weeks of gestation. Placenta is pale and the microscopic features are partly different from those reported in diabetes mellitus. No specific clinical symptoms are described but maturation defect can lead to acute placental dysfunction revealed by signs of acute peripartum hypoxia or even by late intrauterine death. The risk of recurrence is estimated at 10%.     

Clinical significance of pregnancies with circumvallate placenta

AIM: This study examined the clinical significance of patients complicated by circumvallate placenta in comparison with patients with a normal placenta. METHODS: Data were collected from 139 singleton deliveries complicated by circumvallate placenta and from 7666 unaffected controls managed at Japanese Red Cross Katsushika Maternity Hospital between 2002 and 2005. RESULTS: The incidence of premature delivery, oligohydramnios, non-reassuring fetal status on cardiotocogram, placental abruption and intrauterine fetal death in patients complicated by circumvallate placenta were significantly higher than those in control patients. The odds ratio of placental abruption in patients complicated by circumvallate placenta was 13.1 (95% confidence limits: 5.65-30.2). CONCLUSION: A circumvallate placenta is associated with a higher incidence of serious perinatal complications such as placental abruption.     

三维能量多普勒超声产前检测胎盘研究进展

胎盘是妊娠期保证胎儿正常生长、发育的重要器官。围产期妊娠并发症．如妊娠期高血压疾病征、妊娠期肝内胆汁淤积症、妊娠期糖尿病会导致胎盘功能异常;不良妊娠结局,如胎儿生长受限、胎儿宫内缺氧、窒息也与之有关。就三维能量多普勒超声的原理、测量指标的相关性研究及其预测不良妊娠结局．检测胎盘异常的价值和发展前景等综述。     

Antiphospholipid Antibodies in Pregnancy

We assessed the relationship between antiphospholipid antibodies and recurrent miscarriage, fetal deaths, and the pregnancy complications--placental abruption, fetal growth retardation and preeclampsia. The subjects were 81 women with a history of 3 or more miscarriages, 62 with a history of fetal death in the index pregnancy, 105 with a poor obstetric history or pregnancy complications and 13 with systemic lupus erythematosus. Antiphospholipid antibodies were found in 41% of women with a history of recurrent miscarriages, 29% with a history of recent intermediate fetal death or stillbirth, 19% with a poor obstetric history and 69% with systemic lupus erythematosus. There is a high incidence of antiphospholipid antibodies in complicated pregnancies. Patients presenting with the above pregnancy disorders should be tested for antiphospholipid antibodies because of the risk conferred on a fetus by their presence and to expand the treatment options.     

Thrombophilia and pregnancy complications

OBJECTIVE: This systematic review examines the strength of the association between thrombophilia and recurrent pregnancy loss and other serious obstetric complications.Study design Electronic databases and manual bibliography searches were used to identify studies evaluating the association between thrombophilia and pregnancy loss, preeclampsia, fetal growth retardation, and placental abruption. RESULTS: Thrombophilic disorders are associated with an increased risk of fetal loss in the majority of case control and cohort studies. The risk is increased throughout pregnancy, but may be higher in the second and third trimester. The common pathologic finding of placental infarction suggests unexplained fetal loss may result from uteroplacental insufficiency and thrombosis. Thrombophilic disorders are not consistently associated with preeclampsia, fetal growth retardation, or placental abruption. Preliminary data suggest prophylactic anticoagulation may improve outcome in thrombophilic women with unexplained recurrent fetal loss. CONCLUSION: Women with thrombophilia have an increased risk of pregnancy loss and possibly other serious obstetric complications, although definition of the magnitude of risk will require prospective longitudinal studies. Preliminary data suggesting prophylactic anticoagulation may improve gestational outcome provide a rationale for prospective randomized trials in thrombophilic women with unexplained recurrent fetal loss.     

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.     

Early preterm delivery due to placenta previa is an independent risk factor for a subsequent spontaneous preterm birth

ABSTRACT: BACKGROUND: To determine whether patients with placenta previa who delivered preterm have an increased risk for recurrent spontaneous preterm birth. METHODS: This retrospective population based cohort study included patients who delivered after a primary cesarean section (n = 9983). The rate of placenta previa, its recurrence, and the risk for recurrent preterm birth were determined. RESULTS: Patients who had a placenta previa at the primary CS pregnancy had an increased risk for its recurrence [crude OR of 2.65 (95 % CI 1.3-5.5)]. The rate of preterm birth in patients with placenta previa in the primary CS pregnancy was 55.9 %; and these patients had a higher rate of recurrent preterm delivery than the rest of the study population (p < .001). Among patients with placenta previa in the primary CS pregnancy, those who delivered preterm had a higher rate of recurrent spontaneous preterm birth regardless of the location of their placenta in the subsequent delivery [OR 3.09 (95 % CI 2.1-4.6)]. In comparison to all patients with who had a primary cesarean section, patients who had placenta previa and delivered preterm had an independent increased risk for recurrent preterm birth [OR of 3.6 (95 % CI 1.52-8.51)]. CONCLUSIONS: Women with placenta previa, who deliver preterm, especially before 34 weeks of gestation, are at increased risk for recurrent spontaneous preterm birth regardless to the site of placental implantation in the subsequent pregnancy. Thus, strict follow up by high risk pregnancies specialist is recommended.     

Obstetric history and the risk of placenta previa

OBJECTIVE: To evaluate secular trends in the occurrence of placenta previa and whether placenta previa is associated with the outcome of previous pregnancies, cesarean section, and sociodemographic factors. DESIGN: A cohort study based on the Medical Birth Registry of Norway. Placenta previa in the second pregnancy was investigated for associations with outcomes in the first pregnancy and sociodemographic factors. RESULTS: In birth orders 1 and 2 the occurrence of placenta previa was 1.2 and 2.2 per 1,000, respectively, with no secular trend. The occurrence increased with maternal age and was lowest in women aged 20-29 years. The recurrence rate was 23 per 1,000 (adjusted odds ratio (OR) of recurrence=9.7). In women with prior delivery at < or =25 gestational weeks the risk of placenta previa was 6.7 per 1,000 (adjusted OR=3.0). In women with prior placental abruption the risk was 5.8 per 1,000 (OR=2.6). In women with prior perinatal death the risk was 4.4 per 1,000 (adjusted OR= 1.8). No independent relationship emerged with socio-economic factors, previous birthweight, and a history of pregnancy induced hypertension. Cesarean section was associated with subsequent development of placenta previa (adjusted OR= 1.3). CONCLUSIONS: We found no secular trends in the occurrence of placenta previa. Placenta previa is associated with previously described risk factors for placental abruption. The increased risk of placenta previa subsequent to placental abruption supports the theory of a shared etiologic factor. However, placenta previa and placental abruption do not share a common etiology in relation to a history of pregnancy induced hypertension, fetal growth retardation, and socio-economic factors.     

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。     

Recurrent spontaneous miscarriages and hyperhomocysteinemia

AIM: Recurrent fetal loss is defined as the number of consecutive miscarriages which is not less than 2 occurred within the 16th week of gestation and it is a very interesting pathology of pregnancy. Further to thrombophilia, very important causes have been identified, since the damage of the vascular system supporting the placenta may cause a deficiency of placenta functions and development, leading to a loss of the conception product, also in a condition of hyperhomocystinemia, causing a damage to the vascular endothelium. Hyperhomocystinemia seems to be a risk factor for artero-venous thrombotic diseases, even not in pregnancy. METHODS: We have examined 40 patients referred to our Institute for unexplained fetal loss (at least 2 consecutive miscarriages within the 16th week of gestation) and the same number of patients who had at least 1 spontaneous delivery with a healthy and alive newborn and none abortion nor fetal death nor abruptio placentae. RESULTS: The mean levels of homocystinemia observed were significantly different in the 2 groups (p = or < 0.05). In the control group the values of plasmatic homocysteine were 10+/-4 micromol/L, corresponding to normal range, while in the other group the values of plasmatic homocysteine were 21+/-6 micromol/L, values certainly elevated, also because during the 1st trimester of pregnancy the levels of homocysteine decrease, reaching the lowest value during the 2nd trimester of pregnancy. In particular, high levels of homocysteine have been found in 25% (10) of women with unexplained early fetal loss. CONCLUSION: Hypercystinemia, as a consequence of an interaction between a primary genetic defect and a nutrition condition (folate deficiency), may be a cause of recurrent miscarriages. Therefore, in these cases, a possible hypercystinemia should be searched and an association of folic acid and vitamin B6, a non teratogenic treatment, should be useful to restore the metabolic picture and to favour the pregnancy outcome.