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Institute of Medicine (US) Committee on Improving Birth Outcomes; Bale JR, Stoll BJ, Lucas AO, editors. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington (DC): National Academies Press (US); 2003.

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Improving Birth Outcomes: Meeting the Challenge in the Developing World.

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4Reducing Fetal Mortality

The major causes of embryonic and fetal death vary over the course of gestation. Fetal deaths that occur late in gestation (after 28 weeks) and involve a potentially viable fetus are amenable to prevention. This chapter therefore focuses on factors that strongly influence late fetal survival, such as maternal health and the management of labor and delivery, and reviews promising interventions to reduce late fetal deaths in developing countries. Many of the interventions described in the previous chapter are also effective in reducing fetal mortality.

An estimated 4 million late fetal deaths1 occur each year, 98 percent of them in developing countries (Save the Children, 2001; World Health Organization, 1996). Despite the magnitude of this public health problem, it has attracted little attention, and information on these deaths is limited. Late fetal deaths are not included in estimations of the global burden of disease, and are not therefore recognized by decisionmakers for their important role in that burden. A substantial proportion of fetal deaths do not have an identified cause. Fetal autopsy, discussed at the end of this chapter, is sometimes useful for this purpose, but is not available in most developing country settings.

Reported fetal mortality rates vary widely, but generally parallel neonatal and maternal mortality. Table 4-1 summarizes fetal death rates reported from several studies in developing countries. Data on fetal death in developing countries may overestimate fetal mortality in hospitals with many referrals or underestimate it if they serve a higher income segment of the population, because such studies are usually based on hospital data only (Saksena and Srivastava, 1980; Gadow et al., 1991; Conde-Agudelo et al., 2000).

TABLE 4-1. Fetal Deaths from Developing Country Studies.

TABLE 4-1

Fetal Deaths from Developing Country Studies.

Many of the studies in Table 4-1 include estimates of fetal death as a component of perinatal mortality, which includes fetal deaths occurring between 22 or 28 weeks' gestation (depending on the source) and birth, as well as neonatal deaths that occur during the first week of life. For infants who die shortly after birth, distinguishing between late fetal and early neonatal deaths can be difficult. These diagnoses depend on the skill and experience of clinical staff, who may differ in their application of the broad definitions of fetal and neonatal death (Golding, 1991). In order to recognize the true magnitude of both neonatal and fetal mortality, each outcome and its attendant risk factors need to be measured as accurately as possible. This report addresses fetal mortality separately from neonatal mortality so that the distinctions between them can be clarified and causes of mortality addressed according to their priority. Surveillance of fetal mortality, along with other pregnancy and birth outcomes, is discussed in Chapter 5.

FACTORS CONTRIBUTING TO LATE FETAL DEATHS

In settings where most women give birth without skilled assistance, fetal mortality is high, and the proportion of fetal deaths that occur during labor and delivery is high (Conde-Agudelo et al., 2000). These are intrapartum fetal deaths (IPFDs) or so-called fresh stillbirths. Such deaths can often be prevented by skilled management of labor and delivery as described in Chapters 2 and 3. However, skilled care is generally not available for home deliveries. As health care services are improved and fetal deaths during labor and delivery are reduced, antepartum fetal deaths (APFDs), which occur before the onset of labor, account for an increasing proportion of late fetal deaths (Kiely et al., 1985); thus in developed countries, only about 10 to 15 percent of late fetal deaths occur in the intrapartum period (Ogunyemi et al., 1998, Kiely et al., 1985). Since intrapartum fetal deaths predominate in most developing countries, their causes and prevention receive particular emphasis in this chapter. Low-cost measures to significantly reduce risk factors for APFDs are also discussed.

Intrapartum Fetal Deaths

Intrapartum fetal deaths (IPFDs) generally result from maternal conditions or obstetric complications, and frequently involve suboptimal management of labor and delivery (Sheiner et al., 2000; Kiely et al., 1985; Stewart et al., 1998; Escoffery et al., 1994). Early recognition and treatment of risk factors can prevent certain fetal deaths. However, the majority of fetal deaths occur in pregnancies considered to be low risk.

Diabetes mellitus

The offspring of women with diabetes tend to be large for gestational age, and therefore at increased risk for intrapartum injury and asphyxia (Gunton et al., 2000; Garner, 1995). Even with improved glycemic control, the fetus is large in 8 to 43 percent of such pregnancies. Smoking among mothers with diabetes increases the risk for fetal mortality (Gunton et al., 2000). Complications for women with diabetes include maternal infections (more common than among healthy women), pre-eclampsia, and diabetic nephropathy (which carries a high risk of hypertension as well), all of which increase the risk of adverse outcomes. Avoiding adverse fetal outcomes requires early dietary advice, an insulin regimen, and consistent monitoring of glucose and maintenance of an optimal level (Garner 1995).

Infections

The risk for IPFD is much higher for pregnancies among women infected with syphilis than in uninfected women (Schulz et al., 1987).

Obstetric complications

Intrapartum hemorrhage. Premature separation of the placenta (abruptio placentae) causes hemorrhage. The separation varies in size from small to complete and the risk of fetal death increases with the degree of placental separation (Ananth et al., 1999).

Hypertensive disease (which includes chronic hypertension, pre-eclampsia, and eclampsia) may be exacerbated by pregnancy or arise for the first time during pregnancy. Hypertensive disease was found to be a major risk factor in analyses of about 15,000 late fetal deaths in Latin America (Conde-Agudelo et al., 2000), almost 600 late fetal deaths in Jamaica (Greenwood et al., 1994), and 93 late fetal deaths in Ghana (Wiredu and Tettey, 1998). In a study in Mozambique, the fetal death rate for 1,275 women with hypertensive disease of pregnancy was 5.7 percent compared with 2.3 percent for the more than 43,000 women without hypertensive disease (Merz et al., 1992). In a study in Shanghai, China, 8,852 of 158,790 pregnancies involved hypertensive disease; 44 percent were classified as moderate or severe, and the adverse outcomes included 48 antepartum fetal deaths and 12 late fetal deaths (Huang, 2001).

Prolonged or obstructed labor. This is one of the most common preventable causes of fetal mortality. It may involve prolonged first or second stage of labor, cephalopelvic disproportion, uterine rupture, or malpresentation. In Zimbabwe, major causes of perinatal mortality were found to include prolonged first- and/or second-stage labor, uterine rupture, and a retained second twin (Aiken, 1992). Although improvements in antenatal, intrapartum, and neonatal care have the potential to reduce perinatal mortality, further study into specific preventive measures is necessary.

Fetal malpresentation, such as breech or transverse lie, has also been associated with increased risk for fetal death in studies in both developing (Conde-Agudelo et al., 2000; Kapoor et al., 1994; Aiken, 1992; Kusiako et al., 2000) and developed (Sheiner et al., 2000) countries.

Multiple pregnancy. Studies of more than 7,000 births in southern Brazil and more than 9,500 births in Jamaica have reported a two- to fourfold higher risk of fetal mortality in multiple pregnancies compared with singleton pregnancies (Barros et al., 1987; McCaw-Binns, 2000).

Cord complications including prolapse, cord around the neck, knots, or other entanglement also contribute to intrapartum fetal death (Sheiner et al., 2000).

Asphyxia

Asphyxia is an important cause of fetal death. Asphyxia can be broadly defined as progressive hypoxaemia and hypercapnia with a significant metabolic acidaemia (Low, 1997; Bax and Nelson, 1993). In the early 1990s, the Jamaican Perinatal Mortality Survey found intrapartum asphyxia to be the cause of 23 percent of fetal deaths in which the fetus weighed at least 2,500 g (Escoffery et al., 1994). The rate of asphyxia is higher in Ghana (56 percent) (Wiredu and Tettey, 1998). Growth-restricted fetuses appear to have a lower tolerance for intrapartum asphyxia (Tuthill et al., 1999).

Birth injury

Birth injury includes preventable and unavoidable mechanical or hypoxic-ischemic injuries suffered by the neonate during labor and delivery. These may include trauma to the head (most significant is intracranial hemorrhage); trauma to internal organs (such as the liver or spleen); injury to the spinal cord or peripheral nerves (most common is brachial plexus injury and most devastating is cord transection); and fractures (to the clavicles and extremities). The predisposing factors include macrosomia (particulaly for diabetic mothers), cephalopelvic disproportion, dystocia, prolonged or obstructed labor, breech presentation, and prematurity. Although injury may occur despite skilled care at delivery, some injuries are the result of inadequate medical knowledge or suboptimal care during labor and delivery. More specific diagnoses can assist efforts to prevent avoidable birth injuries.

Escoffery and coworkers (1994) found evidence of birth trauma in 22 percent of the IPFDs they examined in Jamaica. In a study in Ghana, birth trauma was found to be responsible for a little more than 5 percent of fetal deaths (Wiredu and Tettey, 1998).

Economic factors

To the extent that low family income limits access to quality health care services, it is a risk factor for IPFD. Family income has been negatively correlated with fetal mortality in India (Saksena and Srivastava, 1980) and Brazil (Barros et al., 1987), with women from the poorest families having a fetal death rate two to four times higher than women from the wealthiest families. A similar relative risk of late fetal death was determined for rural women (who tend to have lower socioeconomic status) compared with urban women in Nepal (Jahn et al., 2000). The risk for late fetal death was significantly higher among wives of unskilled laborers (such as subsistence farmers) in Papua New Guinea (Amoa et al., 1998). In a large study of over 850,000 hospital births in 11 Latin American countries, the late fetal death rate was almost twice as high in free hospitals that serve mainly low-income women as in hospitals requiring payment for services (Gadow et al., 1991). This difference may in part reflect a lower quality of care provided to patients who do not pay for services.

Antepartum Fetal Deaths

The risk factors reported for APFDs include maternal conditions, obstetric complications, and advanced maternal age. Some studies, described below, also indicate that inadequate antenatal care, smoking, high parity, and low socioeconomic status increase the risk for APFD.

Hypertensive disease of pregnancy

Hypertensive disease was found to be a major risk factor for APFD. In Sri Lanka, hypertensive disease was associated with 32 percent of antepartum deaths, the majority of which occurred after 31 weeks of gestation (Lucas and Ediriweera, 1996). Hypertension may result in uteroplacental insufficiency, abruptio placentae, or placental infarction—all risk factors for late fetal death.

Antepartum hemorrhage

This was shown to be one of the most important risk factors for fetal death in studies in Latin America (Conde-Agudelo et al., 2000), Jamaica (Greenwood et al., 1994), and Ghana (Wiredu and Tettey, 1998).

Diabetes mellitus

It is well known that maternal diabetes mellitus increases the risk of intrauterine fetal death (Garner, 1995; Casson, 1997; Hawthorne et al., 1994; Mondestin, 2002; Platt et al., 2002). Although the exact cause of fetal death is unknown, uteroplacental insufficiency, vascular disease, and hypertension associated with diabetes increase risk of death. In addition, congenital malformations in diabetic pregnancies also contribute to increased risk of late fetal death. Several studies have shown that diabetes in pregnancy is associated with hyptertension (Cundy et al., 2002) or with hypertensive disorder of pregnancy (Sibai et al., 2000). Maternal hypertension associated with diabetes may result in fetal compromise earlier in gestation and is particularly worrisome (Lagrew et al., 1993). Early recognition of diabetes mellitus in pregnancy and control of maternal glucose levels can reduce fetal mortality and other complications in affected pregnancies (Langer and Conway, 2000).

Sickle cell disease

This inherited disorder occurs worldwide with the highest incidence in malaria-endemic areas of Africa. Sickle cell disease is associated with an increased risk of fetal mortality, presumably due to placental infarcts (Mahomed, 2003). This risk can be substantially reduced with appropriate antenatal care and management of labor and delivery (Sun et al., 2001; Smith et al., 1996); however, this level of care is not generally available in the countries where sickle cell disease is most prevalent.

Infections

Fetal mortality is associated with a variety of maternal infections including sexually transmitted diseases, bacterial infections of the genitourinary tract, and rubella2 (Goldenberg et al., 1997; Gibbs, 2002).

Syphilis, like rubella, Toxoplasma, and cytomegalovirus, can cause transplacental infection of the fetus. Although a rapid serological test allows on-site diagnosis so that a highly effective treatment of penicillin can be initiated immediately, there continues to be a high level of infectious maternal syphilis in several countries (Hira et al., 1990). The prevalence of syphilis among women attending antenatal clinics is 4 to 16 percent in several countries of Africa and the Caribbean (Hira et al., 1990; Schulz et al., 1987; Prabhakar et al., 1991; McDermott et al., 1993). Untreated syphilis has been shown in several studies to increase the risk of fetal death (de Aquino, 1998; Osman et al., 2001; Schulz et al., 1987; McDermott et al., 1993). In Malawi, a longitudinal population-based study found a population-attributable risk (PAR) for syphilis of 26 percent among mothers who had experienced a fetal death. For antepartum fetal deaths, the PAR was 38 percent for syphilis (McDermott et al., 1993). Syphilis was the attributed cause of 10 percent of late fetal deaths in a case-control study of 315 consecutive late fetal deaths in Papua New Guinea (Amoa et al., 1998).

Other bacterial infections—symptomatic or asymptomatic—are an important risk for late fetal death (Maleckiene et al., 2000). Various reproductive tract infections have been associated with preterm spontaneous labor (Brocklehurst et al., 2002) and rupture of membranes, which can result in fetal death. Infection of normally sterile sites like amniotic fluid, interior of the placenta, and fetal blood can be life threatening (Maleckiene et al., 2000). Chorioamnionitis or amniotic fluid infection has been identified as an important cause of fetal death in several studies in developing (Naeye et al., 1977; Ross et al., 1982, Moyo et al., 1996; Folgosa et al., 1997; Matthews et al., 2001) and industrialized (Tolockiene et al., 2001) countries.

HIV. A systematic review of maternal HIV infection and perinatal outcomes (Brocklehurst and French, 1998) suggests a weak association in developing country studies when there is an attempt to control for confounding. Studies to date have not provided good data on the disease stage of women or their immune function.

Viral hepatitis. Viral hepatitis is a common cause of liver disease during pregnancy and is a cause of fetal death (Michielsen and Van Damme, 1999).

Obstetric complications

Placental abruption, oligohydramnios, and umbilical cord complications have been identified as important risks for APFD in hospital-based, retrospective studies in developed countries (Sheiner et al., 2000; Oron et al., 2001; de Aquino et al., 1998; Ananth et al., 1999). The risk of late fetal death rises steeply when more than half the placenta becomes separated. Hypertensive disease of pregnancy, tobacco use, and drug use are all risk factors for placental abruption (Ananth et al., 1999).

Multiple pregnancy. In Jamaica, antepartum fetal deaths were found to occur about twice as frequently among twins as among singletons (Ashley et al., 1994b).

Prolonged pregnancy is defined as a pregnancy that lasts 42 weeks or more. Developed country studies have shown that prolonged pregnancy increases the risk of fetal death (Hollis, 2002). This risk is increased for growth restricted fetuses; growth restriction itself is an independent risk factor (Divon et al., 1998). In terms of numbers of fetal deaths, however, many more fetuses die between 37 and 42 weeks than after 42 weeks. In low-resource settings, the date of conception is frequently not known, which limits the ability to understand the role of prolonged pregnancy in these populations.

Congenital malformations3

These have been found to account for 6 percent of fetal deaths in Jamaica (Ashley et al., 1994a) and almost 8 percent in Zimbabwe (Aiken, 1992). As fetal mortality due to more preventable causes decreases, the proportion of fetal deaths associated with malformations increases (De Galan-Roosen et al., 1998).

Maternal age and parity

Several studies show an increase in fetal deaths with advanced maternal age (Fretts et al., 1995; Huang, 2000; Andersen et al., 2000; Seoud et al., 2002; Sheiner et al., 2000; Amoa et al., 1998; Khandait et al., 2000). Data from India (Saksena and Srivastava, 1980), Brazil (Barros et al., 1987), and Mexico (Bobadilla-Fernandez, 1986) indicate that fetal death rates are lowest among teen mothers and rise with maternal age. Risk ratios vary from 2 to 4 in the oldest versus the youngest age groups. Other studies have found a U-shaped relationship between maternal age and fetal mortality, with the youngest and oldest mothers faring worst (de Aquino et al., 1998; Andersen et al., 2000; Onadeko et al., 1996; Stanley and Straton, 1981; Murphy et al., 1987; Ahlenius and Thomassen, 1999). Multivariate analyses indicate that the high fetal death rates sometimes observed among teenage mothers may result from social and behavioral influences, rather than a specific biological effect of young maternal age although biological factors can have an influence in very young mothers (Bacci et al., 1993; Hardy et al., 1987; La Guardia et al., 1989). The relationship between maternal parity and fetal mortality is unclear. It is often difficult to separate the effects of advanced maternal age and multiparity (Oron et al., 2001). By contrast, another study shows an association between primiparity and multiparity greater than three and fetal mortality (Huang et al., 2000), and a few studies from industrialized countries have found no association between parity and risk for fetal death (Ahlenius and Thomassen, 1999).

Obesity

Excessive prepregnancy weight has been consistently shown to increase the risk for late fetal death (Conde-Agudelo, 2000; Huang et al., 2000). This relationship remains after controlling for maternal age and excluding maternal diabetes and hypertensive disease.

Social and economic factors4

In both developed and developing countries, low socioeconomic status increases risk of late fetal death. Multivariate analysis of Jamaican data shows social and economic factors to be associated with antepartum fetal deaths. These factors include single motherhood (compared with married or common-law relationships), women assessed by midwives as malnourished, and women living in households that share toilet facilities—an indicator of relatively lower socioeconomic status (Greenwood et al., 1994; Huang, 2000; Stephansson et al., 2001).

Additional factors

The following have been associated with APFD but have yet to be established as significant risk factors for fetal death:

Alcohol consumption. Heavy alcohol consumption during pregnancy has been associated with fetal alcohol syndrome,5 fetal alcohol effects, and increased fetal and neonatal mortality (Jacobson et al., 1993; Faden et al., 1997; Sulaiman et al., 1988; Warren and Bast, 1988). There are no conclusive data on the minimum amount of alcohol ingestion during pregnancy that produces adverse effects in the developing fetus (Roebuck et al., 1999). If a pregnant woman drinks, on average, more than five drinks per occasion once or twice a week, growth, intellectual and behavioral problems short of full-blown fetal alcohol syndrome can occur in the offspring. Calculating in a manner analogous to environmental and food contaminants, one drink every 10 days or less might be considered safe and if it happens, the woman may be reassured. However, alcohol is a neurotoxicant and pregnancy is a very vulnerable time and the deleterious effects are lifelong for the child. Thus minimal to no consumption of alcohol during pregnancy is the best course to follow (Jacobson and Jacobson, 1994, 1999).

Two studies of large populations have addressed the effect of maternal alcohol consumption on fetal mortality for a range of drinking levels, and found an association between maternal alcohol consumption and fetal mortality (Faden et al., 1997; Kesmodel et al., 2002). The first, a retrospective study involving nearly 10,000 live births and about 3,300 fetal deaths in the United States, found that women who consumed more alcohol also smoked more, and were younger and less educated than those who consumed no alcohol or a lower level. Multivariable logistic regression nevertheless showed a significant association of alcohol consumption and fetal death (Faden et al., 1997). The second study, a prospective study in Denmark of nearly 25,000 pregnancies, analyzed the deaths of 116 fetuses of at least 28 weeks' gestation. In this population, the risk of late fetal death for women who consumed five or more alcoholic drinks (each the equivalent of a bottle of beer or glass of wine) per week was found to be nearly three times higher than for those who consumed less than one drink per week (Kesmodel et al., 2002). This result was adjusted for smoking habits, caffeine intake, age, prepregnancy body weight, marital and occupational status, education, parity, and sex of the fetus. The alcohol-associated risk for fetal death was attributed in large part to uteroplacental dysfunction.

Smoking. Several large studies, all conducted in industrialized countries, have found smoking during pregnancy to be a risk factor for late fetal death (Wisborg et al., 2001; Cnattingius et al., 1988; Meyer and Tonascia, 1977; Meyer et al., 1976; Kleinman et al., 1988; Tuthill et al., 1999; Ahlenius and Thomassen, 1999). The association between smoking and fetal death is most likely explained by placental complications and effects on fetal growth.

A study in Sweden of more than 280,000 births, which controlled for confounders, found that smoking increased the risk of fetal death by 40 percent during the third trimester and doubled the risk for mothers who smoked and were aged 35 years or more (Cnattingius et al., 1988). A study of more than 25,000 deliveries in Denmark concluded that continuing to smoke one or more cigarettes per day beyond 16 weeks' pregnancy increased the risk of late fetal death twofold, after adjustment for numerous factors including maternal age, weight, parity, marital and socioeconomic status, and alcohol and caffeine intake (Wisborg et al., 2001). A case-control study of more than 600 late fetal deaths in Wales found that maternal smoking was associated with an increased risk (odds ratio [OR] of 1.72) of fetal death and, most strongly (OR of 2.07), with placental abruption (Tuthill et al., 1999). A similar association between cigarette smoking and placental abruption was found in a prospective Canadian study of more than 87,000 pregnancies (Ananth et al., 1996).

Illegal drug use. Assessing the health risks associated with a particular drug is complicated by the unhealthy lifestyle of many drug users, who frequently use other drugs, tobacco, and alcohol, as well as by the difficulty of obtaining accurate data on individual exposure (Lutiger et al., 1991; Richardson et al., 1993). A meta-analysis of cocaine use, including two studies reporting fetal death as an outcome, yielded a combined odds ratio of 6 (95 percent [CI] 1.2–31.5) for fetal death among cocaine users compared with nonusers (Lutiger et al., 1991). This risk may be due to the association of cocaine use with fetal growth restriction, preterm delivery, and placental abruption (Handler et al., 1991). Studies of cannabis use in pregnancy have failed to show a relationship between antenatal exposure and fetal death (Richardson et al., 1993; Fergusson et al., 2002).

Anemia, highly prevalent in pregnant women in developing countries (Beard, 2000), can result from the increased demands of pregnancy for iron, folic acid, and other micronutrients. The condition may be exacerbated by inadequate diet, malaria, and helminthic infestation. Randomized control trials on the effect of daily supplements to pregnant women of iron alone or iron (100 milligrams) and folic acid (350 milligrams) have been reviewed (Mahomed, 2000, 2002), but found to provide inadequate information on fetal outcomes. These trials are further limited by their rarely being undertaken in the communities where iron and folate deficiency are common (Mahomed, 2002). Two additional reviews reached similar inconclusive findings about the ability of iron or iron and folic acid supplementation6 during pregnancy to prevent fetal death (Xiong et al., 2000; Rasmussen, 2001). There is little information available, particularly in populations where these micronutrients are limited (Mahomed, 2000), and more research is needed.

Malaria contributes to antenatal anemia but has not been shown to be a risk factor for fetal mortality (Luxemburger et al., 2001). Regular treatment with antimalarials, while associated with fewer episodes of severe anemia and fever in the mother, and with higher average birth weights, has not been shown to change perinatal mortality, even in studies of women of low parity (Garner and Gülmezoglu, 2000). Placental malaria infection was not associated with increased perinatal mortality in a prospective study in Malawi (McDermott et al., 1996).

Nutritional deficiencies. Poor maternal nutritional status is associated with adverse birth outcomes (Kramer, 1987; Pojda and Kelley, 2000), but the association with fetal mortality is less clear. A meta-analysis of the effect of dietary supplementation during pregnancy showed that it improved fetal growth and may reduce risk of fetal death (Kramer, 2002). This analysis is based on controlled clinical trials that used balanced supplements, defined as those in which protein contributes 25 percent or less of the total energy content. Most trials were able to provide only a modest increase in net energy intake, and only three trials provided data on fetal mortality.

A controlled trial in Gambia (Ceesay et al., 1997) provided a higher energy supplement (about 1,000 kilocalories) to chronically undernourished pregnant women and significantly reduced fetal deaths; the odds ratio was 0.47 (0.23 to 0.99, P<0.05). Further controlled trials are needed to confirm the benefits of increased dietary consumption on perinatal outcomes in a range of settings. However, given the importance of maternal nutrition before and during pregnancy for other aspects of pregnancy outcomes, lack of findings with respect to fetal death should not preclude the implementation and evaluation of potentially effective interventions to improve maternal nutritional status in developing countries.

Whether deficiencies of micronutrients other than iron and folic acid (discussed above and in detail in Chapter 6) increase risk of fetal death has yet to be established. Deficiencies in zinc and other micronutrients are associated with a broader range of adverse birth outcomes (Black, 2001). Their potential roles in fetal health warrant further study (Fawzi et al., 1998; Chappell et al., 1999).

INTERVENTIONS

De Muylder (1989), who systematically investigated perinatal deaths in a district of Zimbabwe, found that 76 percent of the fetal deaths he reviewed were potentially preventable. Many late fetal deaths were found to be complicated by conditions that are amenable to treatment: hypertension, diabetes, syphilis, or amniotic fluid infection. Better health care—to diagnose and manage maternal diseases that put the fetus at risk, to diagnose acute conditions such as intrauterine infection or hypertension, and to respond to danger signs in a timely manner—would improve fetal survival.

The interventions discussed below target late fetal mortality (beyond 28 weeks' gestation). They emphasize the prevention of IPFD, as it is generally understood that these deaths, which predominate in settings where fetal mortality rates are highest, are more easily prevented than APFDs (Sheiner et al., 2000; Kiely et al., 1985).

Intrapartum Care

The greatest influence of health care on fetal mortality occurs during labor and delivery. Effective referral systems for managing pregnancy complications through basic and comprehensive essential obstetric care are critical to improving all birth outcomes (see Chapter 5). In order to reduce IPFDs, facilities for basic essential obstetric care should monitor labor; manage major obstetric complications, such as severe pre-eclampsia and eclampsia, obstructed labor, and hemorrhage; and address other complications, such as diabetes mellitus, that are associated with high rates of fetal mortality.

Facilities offering comprehensive essential obstetric services can reduce fetal deaths by providing cesarean delivery and blood transfusion, in addition to the services discussed above under basic essential obstetric care. Women with medical complications (e.g., heart disease, sickle cell anemia, diabetes) or poor obstetric history (e.g., previous preterm delivery, fetal or neonatal death, intrauterine growth restriction, malpresentation, ante- or postpartum hemorrhage, eclampsia, or uterine scars) are at high risk of a recurrence of these complications and should plan skilled assistance for delivery, preferably in a hospital that provides comprehensive essential care for labor and delivery.

Many obstetric and maternal complications that may be best treated earlier in pregnancy can still be managed successfully by a skilled birth attendant (physician, midwife, or nurse). Thus, where resources are limited, the most cost-effective means of reducing late fetal mortality is through skilled attendants who can implement the following key interventions:

Detection and management of fetal distress

Fetal monitoring allows early detection of the compromised fetus and alerts the birth attendant to the need for a prompt delivery. The use of tools such as kick charts may be tested in settings where inadequate hygiene increases the risk of infection associated with vaginal examinations. For the induction of labor, intravaginal misoprostol can serve as an effective, low-cost alternative to intravenous oxytocin infusion (Fletcher et al., 1993), particularly in women with severe pre-eclampsia (Hofmeyr, 1998).

Detection and management of prolonged or obstructed labor

Studies have concluded that IPFDs due to asphyxia or trauma can be reduced with adequate monitoring of labor and prompt management of the problems that arise (Wildschut et al., 1990; Escoffery et al., 1994). Active monitoring of the progress of labor with the partograph (see Chapter 2) has been shown effective in alerting skilled birth attendants to obstructed or prolonged labor, which can then be managed to prevent fetal death (Dujardin et al., 1992; World Health Organization, 1994). However, since the partograph necessitates repeated vaginal examinations, good hygiene is a prerequisite for its use.

Detection and management of malpresentation

Breech presentation is associated with increased risk of fetal mortality. Some of the increased mortality reflects the tendency of fetuses with certain birth defects (e.g., neurologic or muscular) to manifest hypotonia and secondarily present as a breech (Jones, 1997). The use of routine external cephalic version (ECV) can safely lower the number of breech deliveries, with minimal risk of fetal or maternal morbidity (Hofmeyr, 2002). Intrapartum deaths due to malpresentation (breech/transverse lie) may be prevented by cesarean section when ECV fails.

Prevention, detection, and treatment of intrapartum infection

The risk of chorioamnionitis can be reduced by limiting vaginal exams, restricting the introduction of anything into the vagina, and ensuring the proper management of women with preterm and/or prolonged rupture of the membranes and/or prolonged labor (Seaward et al., 1997, 1998). If a woman does develop an intrauterine infection, early detection followed by prompt antibiotic treatment is necessary to prevent the infection from becoming life threatening to the mother and/or fetus. Fever during labor, uterine tenderness, and foul-smelling amniotic fluid all suggest intrauterine infection.

Preconceptional and Antenatal Care

Family planning

Chromosomal abnormalities such as Down syndrome can be reduced by discouraging women from bearing children after they reach 35 years of age and by ensuring that these women and their partners have ready access to permanent methods of family planning (e.g. tubal ligation or vasectomy). These methods should also reduce the number of fetal deaths due to chronic medical disorders associated with advanced maternal age, such as hypertension and diabetes.

Antenatal care

Severe complications often begin earlier in pregnancy and, if recognized, can be addressed by early treatment, which provides the best protection against fetal death (Sheiner et al., 2000; Kiely, 1985). Lack of antenatal care is associated with a marked increase in late fetal deaths (Conde-Agudelo, 2000). Early initiation of antenatal care (before 20 weeks of gestation) provides the best opportunity to identify and address risk factors for fetal mortality. Educational programs are needed to convince all pregnant women to obtain key antenatal services (De Muylder, 1989). The following antenatal services can significantly reduce both antepartum and intrapartum fetal deaths:

Detection and treatment of syphilis. Screening for and treatment of syphilis is a cost- effective means of reducing fetal deaths (Temmerman et al., 2000). Universal screening of pregnant women and immediate treatment (at the same visit) for those infected is the most effective means to achieve this goal (Delport and van den Berg, 1998; Patel et al., 2001). Women at high risk for syphilis should be screened again in the third trimester.

Detection and management of hypertensive disease of pregnancy. There is no proven treatment for preventing or delaying hypertensive disease of pregnancy. Effective management may require early delivery for women with severe hypertension and proteinuria. When possible this should occur after 32 weeks' gestation, when the risk of neonatal mortality is lower. It is more difficult to save the fetus when hypertension is associated with placental abruption.

Management of sickle cell disease. Blood transfusions in patients with sickle cell disease (SCD) can dilute their circulating sickle hemoglobin levels and maintain hemoglobin levels at 60-70 percent of the normal level, which reduces pain crises and severe anemia. Blood transfusion in the countries where SCD is prevalent is expensive, and blood supplies may be limited and contaminated with infectious pathogens. A Cochrane review compares SCD management using regular transfusions with selective blood transfusion (only when hemoglobin fell below 6 g per dL). It found the data inadequate for identifying the ideal approach and suggested that hemoglobin may need to be maintained at a slightly higher level (Mahomed, 2003). A study in Benin suggests that practical, inexpensive approaches in conjunction with selective blood transfusions can significantly lower fetal mortality (Rahimy et al., 2000). Since SCD has serious health consequences for women during pregnancy, counseling provides strategies to reduce the risk of an acute event: ways to improve nutritional status with local foods; supplementation with iron, folate, and vitamins; maintaining hydration through high fluid intake; prophylaxis against Plasmodium falciparum malaria; and early detection of bacterial infection (Rahimy et al., 2000).

Detection and Management of Diabetes. Identification and management of women with pre-gestational diabetes improves pregnancy outcome. Screening for gestational diabetes is appropriate for women at high risk due to a previous large for gestational age infant, previous unexplained fetal death, previous congenital malformation, or obesity. Cesarean section, where safely available, may be needed for large for gestational age infants if there is failure of the normal progression of labor.

Recognition of Fetal Deaths

Fetal deaths often go unacknowledged or unrecorded in developing countries, which hinders attempts to adapt interventions and set health care priorities to meet local needs. In Jamaica, for example, researchers found that only 13 percent of late fetal deaths and 25 percent of infant deaths had been registered, compared with 94 percent of live births (McCaw-Binns et al., 1996). In Thailand, a comparison of official records with a community-based survey showed that only 55 percent of infant deaths and none of the late fetal deaths recorded in the survey had been officially registered (Lumbiganon et al., 1990).

Obtaining accurate measures of both fetal and neonatal mortality will require renewed efforts to record all births and accurately assign deaths as fetal or neonatal. Only when the full magnitude and causes of fetal and neonatal mortality are established can policy makers and health professionals identify and implement appropriate health services. Chapter 5 describes strategies for the surveillance of all pregnancy outcomes; the measures described here represent key steps toward establishing surveillance of fetal death.

Autopsy and fetal death audit

A well-performed autopsy may be the sole means of establishing diagnoses in fetal deaths, and is likely to contribute information that differs from clinical findings (Bendon, 2001; Magee, 2001; Tennstedt et al., 2001; Meier et al., 1986; Porter and Keeling, 1987). Congenital anomalies may not be grossly apparent and postmortem findings can contribute to genetic counseling of parents on their fetal loss and future pregnancies (Doyle, 2000; Berger, 1978), and to subsequent monitoring of patient care. In addition, examination of the placenta may help elucidate the cause of death (Naeye, 1992). Autopsies are not widely available in developing country settings.

Classification systems

Unlike most systems for classifying perinatal deaths, the Wigglesworth (1980) system does not rely on autopsy data (Hey et al., 1986). This overcomes a difficult challenge for many developing country settings. A modified form of this method, which permits the classification of fetal deaths, can be used to analyze trends in fetal death and identify critical needs (Keeling et al., 1989). For example, studies using this system in Zimbabwe (De Muylder, 1989) and Jamaica (Ashley et al., 1994a) found asphyxia to be a major cause of fetal death, suggesting the need to improve obstetric monitoring and resuscitative procedures (Golding, 1991).

RECOMMENDATIONS

Recommendations 1, 2, and 4, in the executive summary and chapter 9 have been developed in other chapters. They also address priority interventions for reducing fetal mortality. Surveillance of fetal deaths is even more limited than for neonatal deaths. Until the magnitude of fetal mortality is established, it is likely to remain high.

RESEARCH NEEDS

As a result of the substantial overlap in the causes of fetal and neonatal mortality, several of the research topics in the previous chapter apply here as well. There are two additional priorities for research:

  • Strategies are needed to determine how to monitor labor and delivery more effectively so as to ensure early recognition of complications in low resource settings.
  • Given the high prevalence of unexplained fetal death in developing countries, autopsy studies in diverse settings could help identify potentially preventable deaths, especially those related to infection.

CONCLUSION

The most significant risk factors for fetal death also profoundly affect maternal and neonatal health. In most developing countries, IPFD accounts for a high proportion of fetal mortality. Skilled management of labor and delivery, including access to emergency obstetric care (see Chapters 2, 3, and 5), could prevent many of these deaths, in addition to those of mothers and neonates. The decrease in intrapartum fetal mortality in developed countries can be attributed to improved obstetric monitoring and management of labor and delivery (Goldenberg et al., 1987). Reducing APFD involves addressing maternal factors such as advanced age, prior fetal loss, infectious disease, hypertension, obesity, and other health problems through focused antenatal programs, comprehensive family planning, and health education, as described in previous chapters.

Continued surveillance and analysis of fetal death, as well as maternal and neonatal mortality and morbidity, will allow communities and countries to adapt interventions to local conditions and set health care priorities. The recommendations and research priorities presented in the next chapter emphasize the need to recognize fetal deaths as part of an overall effort to improve birth outcomes.

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Footnotes

1

For this statistic, late fetal deaths are those that occur after 22 (not 28) weeks of gestation.

2

Rubella is discussed in the companion report, Reducing the Impact of Birth Defects: Meeting the Challenge in the Developing World (Institute of Medicine, 2003).

3

Discussed in the companion report, Reducing the Impact of Birth Defects: Meeting the Challenge in the Developing World (Institute of Medicine, 2003).

4

The committee recognizes that female feticide, which generally occurs early in pregnancy, accounts for significant numbers of fetal deaths. In several countries, diagnostic techniques have been used increasingly to determine gender, followed by termination of pregnancy if the fetus is female (Sheth and Malpani, 1997; Imam, 1994; Xu et al., 1997). Preventing such testing is likely to be difficult (Sheth and Malpani, 1997). In some communities, the male to female sex ratio has increased dramatically (Booth et al., 1994). Female infanticide, which can occur shortly after birth, also contributes to deaths recorded as fetal and to the changing ratio of males and females in some populations.

5

For more information, see appendix B and the companion report, Reducing the Impact of Birth Defects: Meeting the Challenge in the Developing World (Institute of Medicine, 2003).

6

This conclusion is specific to the use of folic acid supplementation solely to prevent fetal death due to maternal anemia. The ability of folic acid supplementation to prevent neural tube defects, which can result in fetal death, is well established, as discussed in the companion report on birth defects (Institute of Medicine, 2002).

Copyright 2003 by the National Academy of Sciences. All rights reserved.
Bookshelf ID: NBK222084
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