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.     

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.     

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.     

Advanced maternal age and risk of antepartum and intrapartum stillbirth

AIM: We sought to assess the risk of antepartum and intrapartum stillbirth subtypes among women of advanced age. METHODS: This is a retrospective cohort study using the Missouri maternally linked data containing births from 1978 to 1997. We examined the impact of maternal age on total, antepartum and intrapartum stillbirth across five maternal age group quintiles (20-24, 25-29, 30-34, 35-39 and >or=40) using mothers aged 20-24 years as the referent category. By means of the Cox proportional hazards regression models we obtained adjusted hazards ratios that quantified the magnitude of association between maternal age and the stillbirth subtypes. RESULTS: The rates of antepartum and intrapartum stillbirth were greatest for older mothers (9.3/1000 and 1.2/1000 respectively) and lowest for gravidas aged 25-29 years (3.6/1000 and 0.8/1000 respectively). After adjusting for potentially confounding characteristics, older mothers still remained at greatest risk for antepartum and intrapartum stillbirth (adjusted hazards ratio = 3.6, 95% confidence interval = 2.9-4.4; and adjusted hazards ratio = 2.7, 95% confidence interval = 2.0-3.6 for antepartum and intrapartum stillbirth respectively). The risks for the two subtypes of stillbirth also increased with ascending maternal age in a dose-dependent pattern. CONCLUSIONS: As the demographic distribution of pregnant women persistently shifts to the right, care-providers will be increasingly confronted with elevated risks for adverse fetal outcomes among older mothers. Our results confirm this phenomenon and add new findings in relation to the elevated risk for intrapartum stillbirth among mothers advanced for age.     

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.     

Alloimmunization in twin pregnancies

Among 7052 patients studied between 1976 and 1982 in a collaborative project on antepartum fetal heart rate monitoring, 337 patients had a previous stillbirth as a reason for testing. Overall a previous stillbirth history significantly increased the risk of having a positive result on a contraction stress test, primarily among hypertensive patients. Patients with a previous stillbirth also had a significantly higher incidence of respiratory distress syndrome in their neonates attributable to premature intervention for maternal indications (primarily among hypertensive women and patients with clinical intrauterine growth retardation). Low Apgar scores were found to be significantly increased in diabetics with previous stillbirths primarily due to neonates with congenital malformations. Premature intervention by labor induction or cesarean section was more common among patients with a previous stillbirth for both maternal indications and abnormal antepartum fetal heart rate studies. Previous stillbirth would appear therefore to be a significant risk factor primarily when associated with a diagnosis of hypertension or clinical intrauterine growth retardation.     

Is advanced maternal age an independent risk factor for uteroplacental insufficiency?

OBJECTIVE: To determine whether maternal age 35 years or older is an independent risk factor for uteroplacental insufficiency and thus an independent indication for antepartum testing. STUDY DESIGN: A retrospective cohort analysis was performed of all deliveries at Los Angeles County-University of Southern California Women's and Children's Hospital between August 1, 1995, and September 1, 2003. Women with documented indications for antepartum testing, fetal anomalies, or delivery prior to 34 weeks were excluded from analysis. Markers of uteroplacental insufficiency included stillbirth, birth weight less than the 10th percentile, fetal distress, cesarean section for fetal distress, oligohydramnios, meconium passage, and 5-minute Apgar score less than 7. RESULTS: Indications for antepartum testing were significantly more common in women 35 years or older (33.2% versus 27.0%). After excluding women with indications for antepartum testing, anomalous fetuses, and women delivering prior to 34 weeks, stillbirth was twice as common in women 35 years and older. However, among stillbirths, growth restriction occurred with similar frequency in the older (28.6%) and younger (25.0%) cohorts. Among live births, 2 markers of uteroplacental insufficiency, intrapartum fetal distress (5.7% versus 4.1%) and cesarean delivery for fetal distress (4.0% versus 2.4%) were significantly more common in the older cohort. All other markers of uteroplacental insufficiency were observed with similar frequency in the 2 groups. CONCLUSIONS: After excluding women with other indications for antepartum testing, fetal anomalies, and delivery prior to 34 weeks, stillbirth was twice as common in women 35 years of age or older as in those younger than 35 years. The increased rate of stillbirth does not appear to be explained by a higher rate of uteroplacental insufficiency.     

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.     

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.     

Epidemiology of fetal death in Latin America

BACKGROUND: To identify risk factors associated with fetal death, and to measure the rate and the risk of fetal death in a large cohort of Latin American women. METHODS: We analyzed 837,232 singleton births recorded in the Perinatal Information System Database of the Latin American Center for Perinatology and Human Development (CLAP) between 1985 and 1997. The risk factors analyzed included fetal factors and maternal sociodemographic, obstetric, and clinical characteristics. Adjusted relative risks were obtained, after adjustment for potential confounding factors, through multiple logistic regression models based on the method of generalized estimating equations. RESULTS: There were 14,713 fetal deaths (rate=17.6 per 1000 births). The fetal death risk increased exponentially as pregnancy advanced. Thirty-seven percent of all fetal deaths occurred at term, and 64% were antepartum. The main risk factors associated with fetal death were lack of antenatal care (adjusted relative risk [aRR]=4.26; 95% confidence interval, 3.84-4.71) and small for gestational age (aRR=3.26; 95% CI, 3.13-3.40). In addition, the risk of death during the intrapartum period was almost tenfold higher for fetuses in noncephalic presentations. Other risk factors associated with stillbirth were: third trimester bleeding, eclampsia, chronic hypertension, preeclampsia, syphilis, gestational diabetes mellitus, Rh isoimmunization, interpregnancy interval<6 months, parity > or =4, maternal age > or =35 years, illiteracy, premature rupture of membranes, body mass index > or =29.0, maternal anemia, previous abortion, and previous adverse perinatal outcomes. CONCLUSIONS: There are several preventable factors that should be dealt with in order to reduce the gap in fetal mortality between Latin America and developed countries.     

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.     

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.     

The effectiveness of antepartum surveillance in reducing the risk of stillbirth in patients with advanced maternal age

Objective

To estimate the effectiveness of antepartum surveillance and delivery at 41 weeks in reducing the risk of stillbirth in advanced maternal age (AMA) patients.

Study design

Retrospective cohort study of all patients managed in one maternal–fetal medicine practice from June 2005 to May 2012. We included all singleton pregnancies delivered at ≥20 weeks of gestation. All AMA patients (age ≥35 years at their estimated delivery date) underwent weekly biophysical profile testing beginning at 36 weeks, as well as planned delivery at 41 weeks, or sooner if indicated. We compared the rate of fetal death at ≥20 weeks and fetal death at ≥36 weeks in AMA vs. non-AMA patients. Fetal deaths due to lethal and chromosomal abnormalities were excluded.

Results

4469 patients met the inclusion criteria: 1541 (34.5%) were AMA and 2928 (65.5%) were non-AMA. Using our AMA protocol for surveillance and timing of delivery, the incidence of stillbirth was similar to the non-AMA population (stillbirth ≥20 weeks: 3.9 per 1000 vs. 3.4 per 1000, p = 0.799; stillbirth ≥36 weeks: 1.4 per 1000 vs. 1.1 per 1000, p = 0.773). When looking at women age <35, age 35–39, and age ≥40, the incidence of stillbirth ≥20 weeks and ≥36 weeks did not increase across the three groups. Our findings were similar when we excluded all patients with other indications for antepartum surveillance.

Conclusions

In AMA patients, antepartum surveillance and delivery at 41 weeks appears to reduce the risk of stillbirth to that of the non-AMA population. Routine antepartum surveillance should be considered in all AMA patients.     

Pregnancy outcomes amongst thalassemia traits

Objective

To compare the pregnancy outcome between pregnancies affected and not affected by thalassemia trait.

Methods

A retrospective case–control cohort study was conducted on singleton pregnant women who attended antenatal care and delivered at Songklanagarind Hospital. All of the participating thalassemia trait pregnant women were diagnosed based on hemoglobin typing and/or DNA analysis. A ratio of around 1–1 was used to compare their pregnancy outcomes with normal pregnant women.

Results

Seven hundred thirty-nine thalassemia trait and 799 normal pregnant women were included in the study. All of the women were Thai nationals living in the Southern Region of Thailand and nearly all of them had spontaneously conceived. Maternal complication rates of gestational diabetes, preterm birth, antepartum bleeding, postpartum bleeding, shoulder dystocia and puerperal morbidity, and the rates of neonatal complications: macrosomia, fetal weight <2,000 g, intrauterine growth restriction (IUGR), stillbirth, low Apgar score (<7) at 1 and 5 min and NICU admission, were not significantly different between the two groups. The rate of pre-eclampsia, however, was significantly different, with RRs of 1.73 (CI 1.01–3.00).

Conclusion

The thalassemia trait condition did not affect the risk of gestational diabetes, postpartum hemorrhage, stillbirth, preterm birth and puerperal morbidity. However, pre-eclampsia should be warranted especially among nulliparous and high-BMI pregnant women.     

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.     

First Birth Cesarean and Risk of Antepartum Fetal Death in a Subsequent Pregnancy

Introduction: To examine the relationship between first birth by cesarean and antepartum fetal death in a subsequent pregnancy in a large, hospital‐based population. Methods : Data for this retrospective cohort study were taken from a database of all women who gave birth at Brigham and Women's Hospital during 4 waves of data collection beginning in 1994 and ending in 2002. We calculated the risk of antepartum fetal death in the subsequent pregnancy for women whose first birth was by cesarean compared to women with a vaginal first birth. Survival analysis was used to examine the influence of gestational age at birth. Results: Of 10,996 women who met inclusion criteria, 22% (n = 2450) had first births by cesarean, and 78% (n = 8546) had vaginal first births. The risk of antepartum fetal death in the subsequent pregnancy for women whose first birth was by cesarean was significantly greater than the risk for women whose first birth was vaginal (odds ratio 2.6; 95% confidence interval, 1.1‐6.2). The relationship between first birth cesarean and antepartum fetal death in a subsequent pregnancy differed by gestational age at birth, with no excess risk among women with a previous cesarean birth who gave birth before 34 weeks’ gestation but with a substantially increased risk for women who gave birth at 34 or more weeks’ gestation (unadjusted hazard ratio = 5.6; 95% confidence interval, 1.6‐19.8). Hazard ratio estimates for the association remained significant in bivariate models when adjusted for maternal height, weight, age, hypertension, and diabetes. Discussion: In these data, first birth by cesarean was associated with an increased risk of antepartum fetal death in a subsequent pregnancy. Our findings suggest that antepartum fetal deaths in subsequent pregnancies might be prevented by avoiding primary cesarean birth.     

Risk factors for antepartum and intrapartum stillbirth: a population-based study

To examine disparities in risk factors for stillbirths and its occurrence in the antepartum versus intrapartum periods. A population-based, cross-sectional study using data on women that delivered singleton births between 20 and 43 weeks in Missouri (1989-1997) was conducted (n = 626,883). Hazard ratios and 95% confidence intervals were derived from regression models and population attributable fractions were estimated to examine the impact of risk factors on stillbirth. Among African Americans, risks of antepartum and intrapartum stillbirth were 5.6 and 1.1 per 1,000 singleton births, respectively; risks among whites were 3.4 and 0.5 per 1,000 births, respectively. Maternal age > or = 35 years, lack of prenatal care, prepregnancy body mass index (BMI) > or = 30 kg/m2, and prior preterm or small-for-gestational age birth were significantly associated with increased risk for antepartum stillbirth among whites, but not African Americans. BMI < or = 18.5 kg/m2 was associated with antepartum and intrapartum stillbirth among African Americans, but not whites. The presence of any congenital anomaly, abruption, and cord complications were associated with antepartum stillbirth in both races. Premature rupture of membranes was associated with intrapartum stillbirth among whites and African Americans, but intrapartum fever was associated with intrapartum stillbirth among African Americans. These risk factors were implicated in 54.9% and 19.7% of antepartum and intrapartum stillbirths, respectively, among African American women, and in a respective 46.6% and 11.9% among white women. Considerable heterogeneity in risk factors between antepartum and intrapartum stillbirths is evident. Knowledge on timing of stillbirth specific risk factors may help clinicians in decreasing antepartum and intrapartum stillbirth risks through monitoring and timely intervention.     

The effects of maternal obesity on perinatal outcomes among those born small for gestational age*

Background: Maternal obesity has been associated with higher birth weight. Small for gestational age (SGA) neonates born to obese women may be associated with pathological growth with increased neonatal complications.

Methods: This was a retrospective cohort study of all non-anomalous singleton neonates born in Texas from 2006–2011. Analyses were limited to births between 34 and 42 weeks gestation with birth weight?≤10th percentile. Results were stratified by maternal pre-pregnancy BMI class. The risk for stillbirth, neonatal death, neonatal intensive care unit (NICU) admission and five?minute Apgar scores?<7 were estimated for each obesity class and compared to the normal weight group. Multivariable logistic regression analyses were performed to control for potential confounding variables.

Results: The rate of stillbirth was 1.4/1000 births for normal weight women, and 2.9/1000 among obese women (p?0.001, aOR: 1.83 [1.43, 2.34]). The rate of neonatal deaths among normal weight women was 4.3/1000 births, whereas among obese women it was 4.7/1000 (p?=?0.94, aOR: 1.10 [0.92, 1.30]). A dose-dependent relationship between maternal obesity and stillbirths was seen, but not for other neonatal outcomes.

Conclusion: Among SGA neonates, maternal pre-pregnancy obesity was associated with increased risks for stillbirth, NICU admission and low Apgar scores but not neonatal death.     

Management and outcome of pregnancy in diabetes mellitus, classes B to R

During the period 1971 to 1975, 260 women with diabetes mellitus, Classes B through R, were delivered of their infants at Los Angeles County Women's Hospital. The plan of patient management included frequent clinic visits and hospitalization to assure good control. A program of intensive antepartum fetal surveillance was begun at 34 weeks' gestation, with the use of daily 24 hour urinary estriol determinations and a weekly contraction stress test (CST). A lecithin/sphingomyelin ratio was evaluated for all patients before elective delivery. The perinatal mortality rate in these diabetic pregnant women was 46 per 1,000 as compared to 24 per 1,000 in the general population. Only three stillbirths occurred in the diabetic group, none within one week of a negative CST. Congenital malformations were responsible for almost half of the neonatal deaths. There were no deaths due to iatrogenic prematurity or trauma. Mean gestational age at delivery was 37.9 weeks and vaginal delivery was the mode for approximately half of the women. Two thirds of the infants did experience some morbidity.