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.     

Gestational diabetes: screening,diagnosis, treatment and management

Gestational diabetes (GDM) is a common medical condition in pregnancy, and is associated with a range of short and long term maternal and infant complications including pre-eclampsia, pre-term birth, caesarean section, stillbirth, macrosomia and large-for-gestational age, neonatal hypoglycaemia, and increased risk of later type 2 diabetes in both mother and offspring. The incidence of complications can be reduced and pregnancy outcomes for these women are generally good with effective management of hyperglycaemia using regular monitoring of blood glucose, antenatal care with a multidisciplinary team, diet and lifestyle intervention, and pharmacotherapy. Risk of recurrence in future pregnancies, and of later development of type 2 diabetes is high in women with GDM. Attention should be given to screening and reducing risk in women who have experienced GDM, with encouragement of breastfeeding, diet and lifestyle intervention, weight management, and possibly metformin.     

Maternal Perception of Fetal Activity and Late Stillbirth Risk: Findings from the Auckland Stillbirth Study

Abstract: Background: Maternal perception of decreased fetal movements has been associated with adverse pregnancy outcomes, including stillbirth. Little is known about other aspects of perceived fetal activity. The objective of this study was to explore the relationship between maternal perception of fetal activity and late stillbirth (≥ 28 wk gestation) risk. Methods: Participants were women with a singleton, late stillbirth without congenital abnormality, born between July 2006 and June 2009 in Auckland, New Zealand. Two control women with ongoing pregnancies were randomly selected at the same gestation at which the stillbirth occurred. Detailed demographic and fetal movement data were collected by way of interview in the first few weeks after the stillbirth, or at the equivalent gestation for control women. Results: A total of 155/215 (72%) women who experienced a stillbirth and 310/429 (72%) control group women consented to participate in the study. Maternal perception of increased strength and frequency of fetal movements, fetal hiccups, and frequent vigorous fetal activity were all associated with a reduced risk of late stillbirth. In contrast, perception of decreased strength of fetal movement was associated with a more than twofold increased risk of late stillbirth (aOR: 2.37; 95% CI: 1.29–4.35). A single episode of vigorous fetal activity was associated with an almost sevenfold increase in late stillbirth risk (aOR: 6.81; 95% CI: 3.01–15.41) compared with no unusually vigorous activity. Conclusions: Our study suggests that maternal perception of increasing fetal activity throughout the last 3 months of pregnancy is a sign of fetal well‐being, whereas perception of reduced fetal movements is associated with increased risk of late stillbirth. (BIRTH 38:4 December 2011)     

Sudden fetal death in women with well-controlled, intensively monitored gestational diabetes.

An intensive antepartum monitoring system for women with gestational diabetes mellitus was evaluated over a 5-year period. Early diagnosis and liberal treatment with insulin was concomitantly followed with non-stress testing: weekly from 28 to 34 weeks' gestation and semi-weekly thereafter. Despite maternal euglycemia and satisfactory antepartum assessment, three fetal deaths occurred within 72 hours of reassuring fetal monitoring. Additionally, 24 (7%) fetuses were delivered on the basis of a low biophysical profile score (less than 6) at term. The stillbirth rate for women with gestational diabetes was 7.7/1000, whereas the stillbirth rate for nondiabetic low-risk patients was 4.8/1000. Women with gestational diabetes continue to be in a high-risk category for antepartum fetal death, requiring intensive monitoring with consideration for timely delivery.     

Subsequent birth outcomes after an unexplained stillbirth: preliminary population-based retrospective cohort study

The objective of this study was to determine whether women who have experienced an unexplained stillbirth have a higher risk of adverse perinatal outcomes in subsequent births. We compared 316 subsequent births to women with a previous unexplained stillbirth, with 3160 births to women with no previous history of stillbirth, matched by year of birth, in the period 1987-1997, from the South Australian perinatal database, using logistic regression analysis. There was no increase in the rate of stillbirth and no statistically significant increase in the rate of perinatal death (OR 1.62 [95%CI 0.63-4.20]) or neonatal death, although larger studies are needed to confirm this. However, after adjusting for age, parity, and hospital category of birth, women who had a previous stillbirth had increased incidences in subsequent births of abnormal glucose tolerance or gestational diabetes (a fourfold increase); induction of labour and elective Caesarean section; fetal distress and postpartum haemorrhage; and forceps and emergency Caesarean delivery and preterm birth, which were independent of induction of labour. Gestational age at birth and birthweight were also significantly reduced, suggesting a need for close monitoring of their future pregnancies.     

The changing pattern of fetal death, 1961-1988.

The aim of this study was to assess any changes in cause-specific fetal death rates in the nonreferred population of a tertiary care unit. The fetal death rate (per 1000 births) among 88,651 births diminished from 11.5 in the 1960s to 5.1 in the 1980s. Fetal death due to intrapartum asphyxia and Rh isoimmunization has almost disappeared. Toxemia and diabetes continue to make similar and small contributions to fetal death rates. There has been a significant decline in unexplained antepartum fetal deaths and in those caused by fetal growth retardation, but no significant change in the death rate due to intrauterine infection or abruptio placentae. During the 1960s, the risk of fetal death was increased in women with hypertension, diabetes, or a history of stillbirth; during the 1980s, only women with a history of insulin-dependent diabetes were at risk. Improved application of current knowledge may help decrease the fetal death rate caused by fetal growth retardation. Reduction in deaths due to abruptio placentae, intrauterine infections, or lethal malformations, as well as unexplained antepartum deaths, appears to depend on better understanding of the etiology of these disorders.     

Maternal blood pressure in pregnancy and stillbirth: a case-control study of third-trimester stillbirth

An immense body of literature on the effects of hypertension on perinatal morbidity and mortality exists, but only a handful of studies have reported adverse outcomes associated with low maternal blood pressure during pregnancy. This study aimed to investigate if there is an increased risk of fetal loss associated with hypotension during pregnancy. A matched case-control study of stillbirth and maternal blood pressure was conducted in which maternal blood pressures for a total of 124 pregnancies culminating in stillbirth were compared with maternal blood pressures in 243 (matched) pregnancies resulting in a liveborn infant. Women whose diastolic blood pressures fell in a borderline range (60 to 70 mm Hg) were consistently at greater risk of stillbirth relative to normotensive pregnancies. Women who had three or more mean arterial pressure values < or = 83 mm Hg during the course of their pregnancy were at nearly twice the risk of stillbirth (odds ratio 1.78; 95% confidence interval [CI] 1.06 to 2.99; P = 0.03). Systolic hypotension was not significantly associated with stillbirth, but proportionately more control women were noted to have systolic hypertension (SBP > or = 130 mmHg) than cases, and the adjusted odds of stillbirth in women who were hypertensive at either their first or last antenatal visit or whose antenatal average SBP was > or = 130 mm Hg were all very close to 0.4 (95% CI 0.37 to 0.43; P = 0.02 to 0.03) relative to normotensives. We concluded that maternal hypotension, particularly borderline hypotension, may be a contributory risk factor for stillbirth. Women with hypertension in pregnancy may now be at a decreased risk of stillbirth as a result of the close care and treatment they receive.     

Antenatal testing: diabetes mellitus

Diabetes complicating pregnancy is a problem for which fetal surveillance testing is considered to be the standard of care. In response to the unacceptable frequency of stillbirth in such pregnancies, fetal testing historically was first introduced to manage women whose pregnancies were complicated by diabetes. Essentially all forms of antepartum testing have been used to assess fetal well-being during the third trimester of pregnant diabetics. The contraction stress test became established as the "gold standard," yet other testing protocols have been used successfully. It is clear that control of diabetes throughout gestation, not just in the later stages, is more important for optimal outcome than is a specific form of fetal testing. Biweekly testing has become the standard and with well-controlled diabetics, allowing the gestation to continue until the onset of spontaneous labor, even when the gestation exceeds 40 weeks, is appropriate management with normal testing.     

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.     

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 influence of maternal smoking habits on the risk of subsequent stillbirth: is there a causal relation?

Objective  Maternal smoking has previously been associated with risk of stillbirth. If women who quit smoking reduce their risk of stillbirth, the hypothesis of a causal association would be supported.
Design  Prospective cohort study.
Setting  Nationwide study in Sweden.
Population  All primiparous women who delivered their first and second consecutive single births between 1983 and 2001, giving a total number of 526 691 women.
Method  A population-based Swedish study with data from the Medical Birth Registry, the Immigration Registry and the Education Registry. Logistic regression analyses were used to estimate odds ratios, using 95% confidence intervals.
Main outcome measure  Stillbirth in the second pregnancy.
Results  Compared with nonsmokers in both pregnancies, women who smoked during the first pregnancy but not during the second do not have an increased risk of stillbirth (OR 1.02; 95% CI 0.79–1.30), while corresponding risk among women who smoked during both pregnancies was 1.35 (95% CI 1.15–1.58).
Conclusion  The result supports that maternal smoking during pregnancy is causally associated with stillbirth risk. Smoking is a preventable cause of stillbirth, and smoking interventions is an important issue in antenatal care.     

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.     

Rescue by birth: defective placental maturation and late fetal mortality

OBJECTIVE: To estimate the incidence and lethality of placental maturation defect, and to determine the impact of the pattern of placental dysfunction on the risk of recurrent stillbirth or maternal disease in later life. METHODS: Questionnaire and archival analysis of fetal deaths from placental dysfunction at 32-42 weeks (1975-1995 in Zurich), classified as chronic (parenchyma loss) or acute (maturation defect of the terminal chorionic villi). Population survey of 17,415 consecutive unselected singleton placentas (1994-1998 in Berlin). RESULTS: Of the 71 stillbirths, 34 were due to parenchyma loss and 37 to maturation defect. Parenchyma loss predominated in the first pregnancy (73.5% compared with 43.2%; P <.05). The risks of recurrent stillbirth and subsequent childlessness did not differ between the two groups. Eleven percent of mothers whose placenta had maturation defect had diabetes in the index pregnancy; none of the other women in the group developed diabetes over the 5-20-year observation period. In the population survey, incidence of maturation defect was 5.7%, and was associated with fetal death in 2.3% of cases. Normal placentas were associated with fetal death in 0.033%. CONCLUSION: Placental maturation defect can be a cause of fetal hypoxia. Although the risk of stillbirth is 70-fold that of a normal placenta, few affected fetuses actually die. The risk of recurrent stillbirth is tenfold above baseline and occurs mostly after 35 weeks' gestation.     

Women's expectations on antenatal care as assessed in early pregnancy: number of visits, continuity of caregiver and general content

BACKGROUND: Antenatal care has undergone continuous development over the past decades, but little is known about women's views and expectations. The objective of this study was to explore women's expectations on antenatal care, preferences regarding number of visits and attitudes to continuity of midwife caregiver in a national sample of Swedish-speaking women. METHODS: All Swedish-speaking women booked for antenatal care during 3 weeks spread over 1 year (1999-2000) were invited to participate in the study. A questionnaire was mailed shortly after the first visit. RESULTS: Three thousand and sixty-one women completed the questionnaire, corresponding to 91% of women who consented to participate after exclusion of reported miscarriages. Checking the baby's health was the most important aspect of antenatal care, followed by checking the mother's health and making the partner feel involved. Seventy per cent preferred to follow the standard schedule of antenatal visits, 23% preferred more and 7% fewer visits. In primiparas, age < 25 years, a previous miscarriage and assisted conception were associated with a wish for more visits; in multiparas, previous miscarriage, previous stillbirth and a previous negative birth experience. A wish for fewer antenatal visit was associated with age over 35 years and unfortunate timing of pregnancy among primiparas, and with having more than two children and unfortunate timing of pregnancy in multiparas. Most women (97%) saw continuity of midwife caregiver during pregnancy as important. CONCLUSION: Women had high expectations of antenatal care in terms of possibilities of preventing fetal morbidity, a result that may reflect worries about the baby's health rather than a realistic assessment of the potential of antenatal care procedures. One-third of the women wanted more or fewer visits than the standard schedule, and special attention should be paid to women with a previous stillbirth, miscarriage or a negative birth experience. The Swedish system with continuity of midwife carer during pregnancy was much appreciated.     

Multivariate analysis of risk factors for stillbirth in Leon, Mexico

BACKGROUND: To identify sociodemographic and clinical risk factors for antenatal fetal death in a developing country setting. METHODS: A case-control study was carried out, including 753 women: 251 had a stillbirth (cases) and 502 had a healthy live birth (controls). Stillbirths were considered as antenatal fetal death after 21 weeks of gestation. Seventeen sociodemographic and clinical risk factors for stillbirth were analyzed. Statistical analysis. Student's t-test or the Mann-Whitney U-test for continuous data and the chi2-test or Fisher's exact test for categorical variables were used. Logistic regression analysis was used to find significant predictors for stillbirth. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated. RESULTS: Three risk factors were significant in the logistic regression model: maternal age (OR 1.04, 95% CI 1.00-1.08), antenatal care (OR 0.1, 95% CI 0.0-0.2) and umbilical cord complication (OR 5.8, 95% CI 3.2-10.2). The whole model had a determination coefficient of 0.280, with a chi2-value of 246.2 (p < 0.001). CONCLUSIONS: In our setting antenatal care should be considered as the cornerstone in the prevention of stillbirth. With adequate antenatal care both women with advanced maternal age and umbilical cord complication could be identified. This finding could be useful for developing as well as developed country settings to avoid the occurrence of stillbirth.     

Antepartum testing for women with previous stillbirth

Women with past histories of stillbirth have been referred for antepartum surveillance since the inception of electronic fetal monitoring. However, this approach was originally based on mid-twentieth century perinatal studies that noted an increase in adverse outcomes in pregnancies subsequent to stillbirth. When these landmark studies were done, Rh immune globulin, ultrasonography, and other important medical advances had not yet occurred. This article discusses whether women who have suffered a past stillbirth remain at increased risk for perinatal mortality and morbidity in future pregnancies and whether antepartum fetal surveillance can reduce the risk of recurrent stillbirth.     

妊娠合并甲状腺功能亢进症对胎儿及新生儿的影响

妊娠合并甲状腺功能亢进症（甲亢）并不十分常见。甲亢容易引发孕产妇的不良预后，同时甲亢本身以及治疗甲亢的药物还可以导致胎儿和新生儿并发症的发生，包括死产、低出生体重、甲状腺肿、甲亢、甲减或远期后遗症等。因此，对于甲亢合并妊娠的孕妇，还要关注胎儿和新生儿有可能受到的影响，及时发现、及时治疗。     

Stillbirth in cases of severe acute maternal morbidity

ObjectiveTo determine the incidence and correlates of stillbirths among women with severe acute maternal morbidity (SAMM).MethodsIn an observational study of 728 women who had SAMM between January 2007 and December 2010 at a referral tertiary health facility in Benin, Nigeria, the incidence of stillbirth, and the clinical and demographic correlates of stillbirth were evaluated.ResultsThe rate of stillbirth among women with SAMM was 210 per 1000 deliveries. The rate among women who had uterine rupture (643 per 1000 deliveries) far exceeded other cause-specific rates of stillbirth. Unbooked status (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.3–3.8), low maternal education (OR, 2.1; 95% CI, 1.2–4.0), vaginal delivery (OR, 8.1; 95% CI, 5.1–13.0), and maternal comorbidity (OR, 12.9; 95% CI, 6.2–26.9) were factors associated with stillbirth after adjusting for confounding variables.ConclusionIn Nigeria, SAMM was found to be associated with an unacceptably high rate of stillbirth. Strategies to improve fetal surveillance among women with SAMM are necessary to address the excessively high incidence of stillbirth among these patients.     

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.     

Stillbirths in Western Australia 1980–1983: Influence of Race, Residence and Place of Birth

All stillbirths in Western Australia from 1980-83 weighing 1,000 g and over were identified from perinatal death certificates, and their causes and demographic correlates described. The stillbirth rate was 4.91 per 1,000 total births; nearly 65% were antepartum, 25% intrapartum and in 10% the time of death was unknown. The cause of death of most stillbirths was unknown (52%) or associated with lethal congenital malformations (13%), antepartum haemorrhage (12%) or maternal hypertension (8%). Whilst Aboriginal women had much higher stillbirth rates (10.80) than non-Aboriginal women (4.57), their patterns of time and causes of death were similar. Both antepartum and intrapartum stillbirth rates were much higher at low birth-weights and low gestational ages in both racial groups. Women living in rural areas who delivered in the metropolitan area had much higher antepartum (11.02) and intrapartum (3.31) stillbirth rates than either rural women delivering in rural areas (1.89 and 1.34) or metropolitan women delivering in the metropolitan area (2.72, 0.98). This reflects the transfer of rural high risk pregnant women or those with fetal death in utero, for delivery in metropolitan specialist hospitals.