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 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.     

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 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.     

Grandmultiparas in modern obstetrics

The objective of this study was to compare incidence of antenatal and intrapartum complications among women who had previously delivered five or more times (grandmultiparas cases, 155) with that of age-matched women with two to three previous deliveries (multiparas controls, 155) from 1998 to 2003. Grandmultiparity was associated with a low socioeconomic status, higher incidence of smoking, and a higher body mass index. Grandmultiparas had approximately 2-fold increased risk of gestational diabetes, hypertensive disorders, malpresentation, and preterm delivery, and a 3-fold increased risk of abruption; none reached statistical significance. No significant differences were found in antepartum hemorrhage, anemia, postdatism, polyhydramnios, or placenta previa. Intrapartum complications (labor induction, nonreassuring fetal heart, primary cesarean delivery, and intrapartum fever) were similar; however, operative vaginal delivery was significantly lower in grandmultiparas cases. Both groups were similar regarding birthweight, macrosomia, intrauterine growth restriction, Apgar scores, and stillbirth rates. Our study shows a trend toward an increased risk of adverse obstetrical outcome in grandmultiparas compared with multiparas independent of maternal age.     

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.     

Prosthetic heart valve and pregnancy. A study of 59 cases

We studied 59 pregnancies in 48 female carriers of prosthetic heart valves. In 44 pregnancies the mother had a metal valve mostly with coumarin therapy and in 15 a bioprosthesis usually without hematologic treatment. In the patients with metal prostheses we had the following maternal complications: 1 maternal death, 3 valve thromboses, 2 heart failures and 1 puerperal hemorrhage. There was also a significantly increased rate of preterm, low birth weight infants and intrauterine growth retardation. Concerning malformations we found only 2 cases of mild nasal hypoplasia. Regarding the complications of bioprosthesis, we had only 1 case of paroxysmal tachycardia and no fetal complications. Comparing the results we came to the conclusion that pregnancy is much better tolerated in patients with bioprostheses and that in patients with metal prostheses the risk is increased if the mother is older than 30 years, if time of replacement is more than 5 years or if there is a history of previous thromboembolism or gravidic heart failure.     

Early fetal growth retardation: obstetric background and recurrence rate

The obstetric background of early fetal growth retardation, leading to intrauterine death between 25 and 34 weeks or to delivery before 34 weeks' gestation, was investigated in a group of 100 women. Hypertensive disorders were the most common causative factor (59%). Other causes included antepartum hemorrhage and congenital anomalies. In 20% of the cases no obvious explanation for the fetal growth retardation could be found. The recurrence rate of fetal growth retardation in 49 women who had a subsequent pregnancy was found to be nearly 50%. In one-third the severity of growth compromise was comparable to that in the previous pregnancy, whereas in the hypertensive group this incidence reached nearly 50%. Because of the poor prognosis in current and subsequent pregnancies, it is suggested that women with early fetal growth retardation should be treated at centers where all obstetric and neonatal facilities are available.     

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.     

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.     

A link between relative hypoglycemia-hypoinsulinemia during oral glucose tolerance tests and intrauterine growth retardation

Early identification of the intrauterine growth-retarded fetus is a key factor in improving associated perinatal morbidity and mortality. We investigated, in a prospective study of 43 patients at high risk of intrauterine growth retardation, the predictive value of a derived glucose index and whether hypoglycemia accompanied by hypoinsulinemia in normotensive patients is associated with intrauterine growth retardation. Our findings suggest that the glucose index and 2-hour plasma glucose concentration appear to be useful antepartum predictors of intrauterine growth retardation in normotensive high-risk pregnancies. There is an apparent link between selective maternal hypoglycemia, hypoinsulinemia, and being small for gestational age. A "flat" glucose tolerance test should be regarded as an abnormal pattern in normotensive pregnancies as it was associated with a twentyfold increased risk of intrauterine growth retardation in this study.     

The risk of intrapartum stillbirth among smokers of advanced maternal age

BACKGROUND/AIM: The effects of advanced maternal age and smoking in pregnancy on fetal survival have previously been reported. However, whether advanced maternal age modifies the relationship between smoking in pregnancy and intrapartum stillbirth remains unknown. We therefore set out to determine the impact of advanced maternal age (> or =35 years) on the association between smoking during pregnancy and intrapartum stillbirth by employing retrospective analysis of birth registry data. METHODS: We used a cohort of singleton births in Missouri from 1978 through 1997 (N = 1,436,628) to compute the risk of total, antepartum, and intrapartum stillbirth in smoking mothers. We categorized mothers into two age groups: "younger" (<35 years), and "older" (> or =35 years). Non-smoking mothers age <35 years were the referent category. Cox regression models were used to generate independent measures of association between intrauterine tobacco exposure and the risk of total, antepartum, and intrapartum stillbirth in each age group. RESULTS: A total of 5,772 counts of stillbirth were identified, yielding a stillbirth rate of 4.0 per 1,000. Approximately 33% (N = 1,900) occurred among older smokers resulting in a stillbirth rate of 9.1 per 1,000. The probability of intrapartum stillbirth was greatest among older smokers, followed by younger smokers and lowest among younger non-smokers (P < 0.01). As compared to non-smoking younger gravidas, younger smoking mothers had a 30% greater likelihood for both antepartum and intrapartum stillbirth (adjusted hazard ratio [95% confidence interval]: 1.3 [1.2-1.4] and 1.3 [1.2-1.5], respectively). Among older smokers the risk for intrapartum stillbirth was three times that of the referent group (adjusted hazard ratio: 3.2, 95% confidence interval: 2.2-4.5). CONCLUSIONS: The risk of intrapartum stillbirth associated with smoking in pregnancy is potentiated by the age of the mother. This information will help policy makers develop targeted smoking cessation campaigns and positively impact quit rates in older mothers.     

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.     

A comparison between umbilical artery velocimetry and standard antepartum surveillance in hospitalized high-risk patients

One hundred forty-six women admitted to the high-risk obstetric unit between November 1987 and December 1988 participated in a study designed to compare Doppler umbilical artery flow studies with standard antepartum testing in the prediction of adverse fetal outcome. A Doppler ultrasound examination was considered abnormal when the average systolic/diastolic ratio was greater than or equal to 4. The antepartum testing consisted of a combined use of nonstress testing and contraction stress testing. If both the Doppler systolic/diastolic ratio and the antepartum testing were abnormal, there was a significantly increased incidence of intrauterine growth retardation (47%), fetal distress necessitating cesarean section (67%), and admission to neonatal intensive care (86%). Doppler umbilical artery flow studies are an important adjunct to antepartum fetal surveillance in high-risk patients but should not determine clinical management when standard antepartum surveillance remains normal.     

Nonstress testing with acoustic stimulation and amniotic fluid volume assessment: 5973 tests without unexpected fetal death

In a 36-month period antepartum testing was performed 5973 times in 2628 women with singleton high-risk pregnancies. The testing scheme involved a modified nonstress test with sound stimulation. Testing was performed twice weekly for patients with diabetes (classes B through R), gestational age exceeding 42 weeks, and documented intrauterine growth retardation, and weekly for other indications. If no spontaneous acceleration was observed within 5 minutes, a single 1- to 2-second sound stimulus was applied to the lower maternal abdomen with an artificial larynx. If necessary, a second sound stimulation was applied within 10 minutes. In addition all patients received ultrasonographic four-quadrant assessment of amniotic fluid volume. The mean testing time was 10 minutes. Only 2% of tests were nonreactive with sound stimulation. Seventeen percent of nonstress tests that were nonreactive with sound stimulation were followed by positive results of a contraction stress test or a biophysical profile score less than or equal to 4. The overall intervention rate was 3%. All fetuses with a single acceleration only eventually met criteria for negative results to a contraction stress test or had a biophysical profile score greater than or equal to 8. There were no unexpected antepartum fetal deaths. Sound-induced accelerations appear to be valid in the prediction of fetal well being, and the use of sound stimulation results in a significant shortening of testing time. Simultaneous assessment of amniotic fluid volume may reduce the risk of fetal death to a negligible level.     

Labor monitoring in high-risk situations

Intrapartum asphyxia is increased in several situations such as intrauterine growth retardation, preterm labor, postdate pregnancy or maternal diabetes. In all these cases, fetal heart rate monitoring should be preferred to intermittent auscultation. Fetal scalp blood pH or lactates can be used to identify fetuses at risk of intrapartum asphyxia. However, fetal scalp blood sampling should not delay delivery in case of severe abnormal fetal heart rate as fetal asphyxia could occur rapidly in theses high-risk pregnancies. Data is insufficient to recommend fetal pulse oximetry or ECG analysis. Research should be undertaken to evaluate their performance in these situations.     

Prenatal diagnosis and management of congenital heart disease

Thirty-two fetuses were diagnosed as having congenital heart disease (CHD). The major indications for level II echocardiography other than suspected cardiac abnormalities were fetal malformations, nonimmune hydrops and cardiac arrhythmia. Only three patients had a previous history of fetal CHD. No false-abnormal diagnosis of severe CHD was made. Aortic arch anomalies represented the major diagnostic problem among the six correct but incomplete diagnoses. Sixty-one percent of the fetuses were growth retarded, thus confirming the severity of their CHD. Chromosomal anomalies and extracardiac malformations were associated in 19% and 44% of the fetuses, respectively. Obstetric management and fetal prognosis in cases of extracardiac malformations were greatly influenced by the diagnosis of CHD. The poorest perinatal outcome was associated with heart failure. The only intrauterine deaths occurred in that group, and only one neonate survived. The outcome was more favorable in neonates without other malformations or heart failure. Four of ten (40%) of those neonates survived, while the overall perinatal survival rate was 24%.     

The association of maternal floor infarction of the placenta with adverse perinatal outcome

Maternal floor infarction of the placenta is a relatively rare disorder that on gross examination is characterized by a thickened gray-yellow maternal floor of the placenta with histologic evidence of massive fibrin deposition involving the decidua basalis and the contiguous villi. This lesion has been associated with fetal death, preterm delivery, and intrauterine growth retardation and is thought to be recurrent. Sixty cases of maternal floor infarction were identified in 48 women. Fetal death occurred in 24 of the 60 cases (40%). Preterm birth occurred in 21 of 36 (58.3%) live-born infants, and 19 of the 35 (54.2%) live-born infants for whom a birth weight was known had evidence of intrauterine growth retardation. Among the 41 multiparous patients in our series there were five documented recurrences (12.2%). Review of the past reproductive history of these 48 patients (196 pregnancies) demonstrated a significant incidence of fetal death (24.1%), intrauterine growth retardation (31.3%), and preterm death (35.4%). The association of fetal death and maternal floor infarction emphasizes the importance of a placental examination with all cases of fetal death and infants with intrauterine growth retardation. Given the risk of recurrence, the identification of maternal floor infarction should alert the clinician to the potential for growth retardation, preterm birth, and fetal death in subsequent pregnancies.     

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.