Characteristics of Fetal Death

Another way to consider the contribution of fetal events on PMR is to look at the infant mortality rate ( Fig. 11-3 ). Although the infant mortality rate includes all deaths of infants younger than 1 year of age, 50% of all infant deaths occur in the first week of life, and 50% of these losses result during the first day of life. The infant mortality rate has fallen progressively and even more steeply over time than the fetal death rate, from 47 per 1000 in 1940 to 6.14 per 1000 in 2010. In 2010 about 24,500 infant deaths (6.14 per 1000 live births) were reported, which included 16,200 neonatal deaths (4.05 per 1000 live births), and 12,900 of these were in the first week of life. In 2010, the leading causes of infant mortality were congenital malformations, deformations, and chromosome abnormalities (21%); disorders related to short gestation and low birthweight, not elsewhere classified (17%); sudden infant death syndrome (8%); and maternal complications of pregnancy (6%). Together, these leading causes accounted for over 50% of all infant deaths in the United States in 2010. Clearly, perinatal events play an important role in infant mortality.

Relative magnitude of components of fetal and infant mortality, United States 2006.

(Data from the Centers for Disease Control and Prevention/National Center for Health Statistics, National Vital Statistics System, August 2012.)

Causes of Fetal Death

In addition to declining frequency in PMR over time, the overall pattern of perinatal deaths in the United States has changed considerably during the past 40 years. Manning and associates suggest that antepartum deaths may be divided into four broad categories: (1) chronic asphyxia of diverse origin; (2) congenital malformations; (3) superimposed complications of pregnancy, such as Rh isoimmunization, placental abruption, and fetal infection; and (4) deaths of unexplained cause. Fretts and colleagues analyzed the causes of deaths, confirmed by autopsy, in fetuses weighing more than 500 g in 94,346 births at the Royal Victoria Hospital in Montreal from 1961 to 1993. The population studied was predominantly white, participated in prenatal care, and included patients from all socioeconomic groups. Overall, the fetal death rate in this group declined by 70%, from 11.5 per 1000 in the 1960s to 3.2 per 1000 during 1990 to 1993. The decline in the fetal death rate in this cohort was attributed to the prevention of Rh sensitization, antepartum and intrapartum fetal surveillance, improved detection of intrauterine growth restriction (IUGR) and fetal anomalies with ultrasound, and improved care of maternal diabetes mellitus and preeclampsia. The role of antenatal diagnosis and management of congenital malformations and aneuploidy is obviously critical to a goal of reducing perinatal morbidity and mortality and will be discussed separately (see Chapter 9 , Chapter 10 , Chapter 27 ).

Fretts and colleagues noted that most of the deaths in the Canadian cohort occurred between 28 and 36 weeks’ gestation and that the diagnosis of IUGR was rarely identified before death. In addition to IUGR, leading causes of fetal death after 28 weeks’ gestation included abruptio placentae and unexplained antepartum losses. Despite a marked fall in unexplained fetal deaths, from 38.1 to 13.6 per 1000, this category was used for more than 25% of all stillbirths. Fetal to maternal hemorrhage may occur in 10% to 15% of cases of unexplained fetal deaths. Fetal deaths caused by infection, most often associated with premature rupture of the membranes (PROM) before 28 weeks’ gestation, did not decline over the 30 years of the study and accounted for about 19% of fetal deaths. Further population-based analyses of the causes of fetal death have confirmed these findings, including a 2011 evaluation by the Stillbirth Collaborative Research Network, which utilized rigorous methods to classify as many “unexplained” fetal deaths as possible.

In summary, based on available data, about 30% of antepartum fetal deaths may be attributed to asphyxia (IUGR, prolonged gestation), 30% to maternal complications (placental abruption, hypertension, preeclampsia, and diabetes mellitus), 15% to congenital malformations and chromosome abnormalities, and 5% to infection. At least 20% of fetal deaths have no obvious fetal, placental, maternal, or obstetric etiology, and this percentage increases with advancing gestational age. Late-gestation stillbirths are more likely to have no identifiable etiology. The ability of our current methods of surveillance to make an impact on the perinatal mortality will depend on the ability of available tests to predict and predate injury and on use of obstetric interventions to prevent adverse outcomes. In one British series, obstetric and pediatric assessors reviewed the circumstances surrounding each case of perinatal death to identify any avoidable factors that may have contributed to the death. Of the 309 perinatal deaths in this population (half fetal and half in the first week of life), 59% were considered to have had avoidable factors, including 74% of normal-birthweight infants with no fetal abnormalities and no maternal complications. Most avoidable factors were found to be obstetric rather than pediatric or maternal and social. The failure to respond appropriately to abnormalities during pregnancy and labor—including results from the monitoring of fetal growth or intrapartum fetal well-being, significant maternal weight loss, or reported reductions in fetal movement—constituted the largest groups of avoidable factors. This characterization of avoidable factors that contribute to perinatal death has been confirmed in additional studies.

Timing of Fetal Death

Another way to classify fetal deaths may be to differentiate those that occur during the antepartum period and those that occur during labor, or intrapartum deaths . Antepartum fetal death is much more common than intrapartum fetal death, and unexplained fetal death occurs far more commonly than unexplained infant death. In a population-based study in the United States in 2007, the antepartum fetal death rate was 3.7 per 1000, compared with 0.6 per 1000 intrapartum fetal deaths. Although most fetal deaths occur before 32 weeks’ gestation, in planning a strategy for antepartum fetal monitoring, the risk for fetal death must be examined in the population of women who are still pregnant at that point in pregnancy. When this approach is taken, the data would suggest that fetuses at 40 to 41 weeks are at a threefold greater risk and those at 42 or more weeks are at a twelvefold greater risk for intrauterine death than fetuses at 28 to 31 weeks. The risks are even higher in multiple gestations as pregnancy progresses. For twin gestations, the optimal time for delivery to prevent late-gestation perinatal deaths is by 39 weeks, and for triplets, 36 weeks. The issue of timing is also illustrated by a recent cohort study of over 75,000 singleton pregnancies with fetal growth restriction, the focus of which was to find the point at which the competing risks of fetal death and neonatal death were in balance, in order to inform delivery decisions. In this cohort, the balance point was 32 to 34 weeks.

Identifying Those at Risk

Some risk factors have a clear etiologic relationship to fetal compromise and death, such as exposures to teratogens or maternal conditions that alter the fetal environment or blood supply or content. Other risk factors—such as epidemiologic factors that include maternal age, race, and body habitus—have a perhaps more complex and less well-understood link to fetal death risk ( Fig. 11-4 ). Common risk factors for fetal death in the United States are listed in Table 11-1 . Many of these conditions can coexist in individual patients, which makes assessment of the contribution of each factor to perinatal mortality a challenge. A recent concept of looking at individual risk factors as part of a “triple risk model” may prove useful in making sense of this challenge, similar to that used to understand contributors to sudden infant death syndrome (SIDS). In this model, proposed by Warland and Mitchell, an interplay exists among maternal, fetal, and placental factors and a stressor. They posit that whereas these factors in isolation may be insufficient to cause fetal death, they may prove lethal in combination ( Fig. 11-5 ). Also necessary to consider is the contribution of these conditions to fetal injury that results in liveborn children with permanent neurologic compromise; this has yet to be determined but is an important alternative outcome to perinatal mortality that deserves further study.

Continuum of certainty in pathophysiology of cause of fetal death. Progressing from left to right on the continuum, levels of certainty increase as to the role of the pathophysiology of a particular condition in causing the fetal death. ALT, alanine aminotransferase; GA, gestational age; SLE, systemic lupus erythematosus.

(Courtesy Professor Gordon Smith. Modified from Reddy UM, Goldenberg R, Silver R, et al. Stillbirth classification: developing an international consensus for research. Executive summary of a National Institute of Child Health and Human Development workshop. Stillbirth Classification of Cause of Death. Obstet Gynecol. 2009;114:901-914.)

Triple risk model in which an interplay of maternal factors, fetal/placental factors, and a stressor contribute to fetal death. Whereas these factors in isolation may be insufficient to cause fetal death, they may prove lethal in combination.

(From Warland J, Mitchell EA. A triple risk model for unexplained late stillbirth. BMC Pregnancy Childbirth. 2014;14:142.)

Maternal Characteristics

Maternal Age

Multiple investigators have found that after controlling for risk factors such as multiple gestation, hypertension, diabetes mellitus, placenta previa and placental abruption, previous abortion, and prior fetal death, women 35 years of age or older have a greater risk for fetal death than women younger than 30 years, and women 40 years or older have an even further increased risk. A J -shaped curve relationship exists between maternal age and fetal deaths, with the highest rates in teenagers and women older than 35 years ( Fig. 11-6 ). The interplay of fetal death, maternal age, and gestational age was demonstrated in a population-based 2006 study in the United States of almost 5.5 million births. In this cohort, compared with their counterparts aged 30 to 34 years at 41 weeks of gestation, women older than 35 to 39 years had the same risk for fetal death at 40 weeks, and women older than 40 years had the same risk at 39 weeks. Only 10% of the women older than 35 years had medical comorbidities, and the results of this study did not change when those women were excluded; this highlights the point that the increase in fetal death risk exists in otherwise healthy older gravidas compared with younger women.

Relationship of fetal death and maternal age across gestation.

(From Reddy UM, Ko CW, Willinger M. Maternal age and the risk of stillbirth throughout pregnancy in the United States. Am J Obstet Gynecol. 2006;195:764-770.)

Maternal Comorbidities

Obstetric Factors

Conclusions

The best use of available antenatal testing modalities may vary according to the risk profile of each individual pregnancy. Discussion of condition to specific testing will be undertaken after review of the individual testing modalities described later.

Fetal State

To be able to diagnose suspected fetal compromise using tests of fetal biophysical state, blood flow, and heart rate, we must be able to appreciate how these parameters appear under normal conditions and in response to suboptimal conditions.

Regarding fetal biophysical characteristics, it must be appreciated that during the third trimester, the normal fetus can exhibit marked changes in its neurologic state. Four fetal states have been identified. The near-term fetus spends about 25% of its time in a quiet sleep state (state 1F) and 60% to 70% in an active sleep state (state 2F). Active sleep is associated with rapid eye movement (REM). In fetal lambs, electrocortical activity during REM sleep is characterized by low-voltage, high-frequency waves. The fetus exhibits regular breathing movements and intermittent abrupt movements of its head, limbs, and trunk. The fetal heart rate in active sleep (state 2F) exhibits increased variability and frequent accelerations with movement. During quiet, or non-REM, sleep, the fetal heart rate slows, and heart rate variability is reduced. The fetus may make infrequent breathing and startled movements. Electrocortical activity recordings at this time reveal high-voltage, low-frequency waves. Near term, periods of quiet sleep may last 20 minutes, and those of active sleep, about 40 minutes. The mechanisms that control these periods of rest and activity in the fetus are not well established. External factors such as the mother’s activity, her ingestion of drugs, and her nutrition may play a role. Specific factors that may decrease fetal movement in the third trimester include fetal anomalies, particularly central nervous system (CNS) anomalies; maternal exposures, including corticosteroids, sedatives, smok­ing, and anxiety; low amniotic fluid volume; and decreased placental blood flow due to placental insufficiency.

When evaluating fetal condition using the NST or the biophysical profile (BPP), the clinician must consider whether a fetus who is not making breathing movements or showing accelerations of its baseline heart rate is in a quiet sleep state or is neurologically compromised. In such circumstances, prolonging the period of evaluation usually allows a change in fetal state, and more normal parameters of fetal well-being will appear.

Regarding regulation of fetal heart rate and blood flow, fetal adaptation to hypoxemia is mediated through changes in heart rate and redistribution of cardiac output. However, changes in fetal cardiac output are generally observed during hypoxemia only with coexisting acidemia. In response to sudden hypoxemia, fetal heart rate slowing and increased variability can be observed initially through vagally mediated chemoreceptor responses. With prolonged hypoxemia (30-60 min), increasing levels of circulating adrenergic agonists and modulation of vagal activity by endogenous opiates lead to a fetal heart rate return to or rise from the previous baseline. Development of acidemia on top of hypoxemia can accelerate the rate of fetal deterioration and amplify the hypoxemia by a shift of the oxyhemoglobin dissociation curve to the right, which further reduces the oxygen-carrying capacity of fetal blood and eventually leads to a redistribution of cardiac output that can be appreciated as a “brain-sparing” effect in the evaluation of fetal blood flow. Redistribution of blood flow in the compromised fetus preferentially preserves perfusion not only to the brain but also to the heart and adrenal glands.

Fetal movement is a more indirect indicator of fetal oxygen status and CNS function, and decreased fetal movement is noted in response to hypoxemia. However, gestational development of fetal movement must be considered when evaluating fetal well-being as marked by fetal activity. Periods of absent fetal movement become more prolonged as gestation advances, and normal fetuses progressively exhibit longer periods of quiescence as the late second and third trimesters advance. Up to and perhaps longer than 40 minutes of fetal inactivity at 40 weeks may be a normal finding, compared with less than 10 minutes at 20 weeks and less than 20 minutes at 32 weeks. Keeping these trends in mind, an abnormal degree or absence of fetal movement can be an appropriate marker for fetal hypoxemia. However, fetal activity levels have been seen in animal studies to adapt to inducement of hypoxemia with a resumption of fetal breathing and body movements after a prolonged period of hypoxemia, especially if induced gradually. Therefore observation of these fetal states during antenatal testing does not guarantee a normoxic fetus.

Maternal Assessment of Fetal Activity

Studies performed using real-time ultrasonography have demonstrated that during the third trimester, the human fetus spends 10% of its time making gross fetal body movements and that 30 such movements are made each hour. Periods of active fetal body movement last about 40 minutes, whereas quiet periods last about 20 minutes. Patrick and colleagues noted that the longest period without fetal movements in a normal fetus was about 75 minutes. The mother is able to perceive about 70% to 80% of gross fetal movements. The fetus does make fine body movements such as limb flexion and extension, hand grasping, and sucking; these probably reflect more coordinated CNS function, although the mother is generally unable to perceive these fine movements. Fetal movement appears to peak between 9:00 pm and 1:00 am , a time when maternal glucose levels are falling. In a study in which maternal glucose levels were carefully controlled with an artificial pancreas, Holden and coworkers found that hypoglycemia was associated with increased fetal movement. Fetal activity does not increase after meals or after maternal glucose administration, but it may increase during exposure to music, as was demonstrated in one novel randomized trial.

The decrease in fetal movement with hypoxemia makes maternal assessment of fetal activity a potentially simple and widely applicable method of monitoring fetal well-being. However, prospective trials of this method for prevention of perinatal mortality have failed to conclusively show benefit. Neldam demonstrated a 73% reduction in avoidable fetal deaths in a prospective trial of more than 1500 women instructed to count fetal movements. In contrast, a subsequent international trial of more than 68,000 women randomized to routine fetal movement assessment versus no formal assessment of fetal activity failed to show a significant reduction in fetal deaths in the group randomized to routine movement counting. Significant differences were noted in the method of fetal movement counting (FMC), the definition of “abnormal” fetal movements, patient compliance with the intervention, and provider response to patients who presented to care as a result of an abnormal fetal movement count in the latter, compared with the former, trial and throughout the literature on this topic. This illustrates the difficulties in validating and reproducing the results of these trials and the uncertain clinical benefit that may be derived from introducing maternal assessment of fetal movement into routine clinical practice. A 2007 Cochrane review of four trials that involved more than 71,000 women concluded that evidence is insufficient to recommend routine FMC to prevent fetal death.

Despite these results, this type of fetal assessment may offer some advantages. Although the range in fetal activity will be wide but normal, with FMC, each mother and her fetus serve as his or her own control. Factors that affect maternal perception of fetal movement are not well understood. Fetal and placental factors that may contribute include placental location, the length and type of fetal movements, and amniotic fluid volume (AFV), although whether AFV affects maternal perception or actual fetal movement is unclear. Maternal factors that may influence the evaluation of fetal movement include maternal activity, parity, obesity, medications, and psychological factors, including anxiety. Studies of these associations have demonstrated conflicting results. About 80% of all mothers are able to comply with a program of counting fetal activity.

Several methods have been used to monitor fetal activity in research and clinical practice. These methods include FMC over a prescribed time period, such as 30 to 60 minutes one to three times daily, or conversely a target number of fetal movements to be counted over a variable time range. A variety of “normal” and “abnormal” FMC results or thresholds have been proposed, to which the patient should be instructed to respond by presenting for further evaluation of the condition of the fetus ( Fig. 11-8 ). These potential triggers for further evaluation include fewer than three movements in 1 hour or no movements for 12 hours, Sadovsky’s “movement alarm signal”; fewer than three movements an hour for 2 consecutive days; or inability to count 10 movements in a 12-hour period, the Cardiff “count-to-10” method advocated by Pearson and Weaver. The count-to-10 method has received wide scrutiny and is used perhaps most frequently in clinical practice. The use of this technique as a screening tool has most recently been reexamined by Froen and associates. In a cohort of 1200 women instructed to start their fetal movement count at the first convenient time of the day, they found that the mean time to count to 10 was less than 10 minutes, compared with significantly longer and more variable average times reported in previous investigations. Noting the variation in defining normal and abnormal patterns and maternal perception of fetal movement as mentioned previously, Froen and associates concluded that significant research is needed to better define the changes in fetal activity patterns and perception associated with good and adverse perinatal outcomes.

Only gold members can continue reading. Log In or Register to continue

Share this:

• Click to share on Twitter (Opens in new window)
• Click to share on Facebook (Opens in new window)

Related

Related posts:

1. Operative Vaginal Delivery
2. Cesarean Delivery
3. Prolonged and Postterm Pregnancy
4. Mental Health and Behavioral Disorders in Pregnancy

Stay updated, free articles. Join our Telegram channel

Join