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Improving Birth Outcomes: Meeting the Challenge in the Developing World (2003)

Chapter: 3. Reducing Neonatal Mortality and Morbidity

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Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
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Summary of Findings: Reducing Neonatal Mortality and Morbidity in Developing Countries

  • An estimated 4 million neonates (aged up to 28 days) die each year. These deaths account for about 40 percent of under-5 mortality and two-thirds of infant (aged up to 12 months) mortality. Ninety-eight percent of neonatal deaths occur in developing countries.

  • The true burden of neonatal mortality in developing countries is unknown because many deaths occur in the home and are not reported. Limited epidemiological research indicates the main causes of neonatal deaths are infections, birth asphyxia, birth injuries, complications of preterm birth, and birth defects.

  • Because complications of childbirth too frequently cause neonatal death, skilled assistance is recommended for all deliveries along with access to the appropriate level of neonatal care when needed.

  • Preconceptional and antenatal care provide an opportunity to reduce risk factors for neonatal mortality and morbidity. These include detection and treatment of maternal infections; immunization of women of reproductive age against tetanus; and counseling on risks to a healthy pregnancy and birth preparedness, emphasizing the importance of a clean and safe delivery assisted by a skilled birth attendant.

  • Clean and safe newborn care should prevent and manage neonatal infections and other illnesses that can otherwise become life threatening. Caregivers must be able to recognize signs of illness, and when they appear, promptly seek appropriate medical assistance.

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
×

3
Reducing Neonatal Mortality and Morbidity

The greatest risk of childhood death occurs during the neonatal period, which extends from birth through the first month of life. About 60 percent of all deaths to children under age 5 and nearly two-thirds of infant deaths (birth to 12 months) occur during the neonatal period (Rutstein, 2000). About two-thirds of all neonatal deaths occur during the first week of life. Current estimates place the annual neonatal death toll at 4 million (Save the Children, 2001).

Approximately 98 percent of neonatal deaths occur in the developing world (World Health Organization, 1996b). The highest annual neonatal rates are in South Asia, where an estimated 51 deaths occur for every 1,000 live births. Each year in South Asia alone, 2 million children die within a month of their birth. By comparison, the rates per 1,000 live births are 42 in Africa, 25 in Latin America, and fewer than 10 in Europe and North America (World Health Organization, 1996b). The burden of neonatal morbidity in developing countries is unknown; however, a recent study of neonatal morbidity in rural India revealed that nearly half of the 763 infants observed developed high-risk morbidities (those with a case fatality greater than 10 percent), and nearly three-quarters suffered low-risk morbidities, some in addition to high-risk conditions (Bang et al., 2001).

CAUSES OF NEONATAL MORBIDITY AND MORTALITY

Most neonatal deaths occur at home, following unsupervised deliveries; thus little accurate information is available as to their causes (Stoll,

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
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FIGURE 3-1 Global estimates of the direct causes of neonatal mortality.

SOURCE: WHO Mother-Baby Package, 1994.

1997). Limited epidemiological research indicates that the principal direct causes of neonatal death are infectious diseases, birth asphyxia, birth injuries, and the sequelae of preterm birth and birth defects (Figure 3-1). During the early neonatal period (0-7 days), the major causes of death are asphyxia, infection, complications of prematurity, and birth defects; infections cause most late neonatal deaths (8-28 days) (Lawn et al., 2001).

This chapter addresses neonatal infections, birth asphyxia, birth injury, hypothermia, and hyperbilirubinemia. Strategies to reduce mortality and morbidity associated with low birth weight are discussed in Chapter 6; those associated with birth defects, in Chapter 7; and those associated with perinatal transmission of HIV, in Chapter 8.

Infectious Diseases

Infections are the major cause of mortality and morbidity in infants under 3 months of age in developing countries (Stoll, 1997). As noted in Chapter 1, more than 20 percent of children born in developing countries acquire an infection during the neonatal period, leading to an estimated 30 to 40 percent of all neonatal deaths (Stoll, 1997; Stoll, 2000). Most of these deaths are caused by acute respiratory infections, bacterial sepsis and/or

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
×

TABLE 3-1 Estimated Global Burden of Disease Due to Major Neonatal Infections

Infection

Estimated No. of Cases

Estimated Case Fatality Rate*

Estimated No. of Deaths

Sepsis

750,000

40%

300,000

Meningitis

126,000

40%

50,400

Tetanus**

355,000

70%

248,000

Acute respiratory infections

2,650,000

30%

800,000

Diarrhea

25,000,000

0.6%

150,000

HIV

550,000

na

na

Total

29,431,000

1,548,400

na = Data unavailable: Most HIV-related deaths occur after the neonatal period.

* Fatality rates may be much higher in developing countries.

** Updated data from World Health Organization, 1999a.

SOURCE: Stoll, 2000 (data from 1995).

meningitis, neonatal tetanus, and diarrhea (Table 3-1). Maternal infections, including sexually transmitted diseases (STDs) such as HIV (the topic of Chapter 8) and syphilis, can be transmitted to the fetus or newborn in utero, through contact during labor and delivery, and in some cases, through breastfeeding.

Sepsis

In many countries, bacterial sepsis accounts for a substantial burden of disease and has a 40% case fatality rate (Stoll, 2000). Early-onset neonatal sepsis (48-72 hours) usually results from organisms acquired from the maternal genital tract during birth and often is associated with maternal complications; late-onset neonatal sepsis (7-28 days) is more likely to be caused by organisms acquired from the environment (Korbage de Araujo et al., 1999; Martius et al., 1999; Moreno et al., 1994; Kuruvilla et al., 1998; Schuchat et al., 2000; Stoll et al., 2002a,b).

Estimates of the incidence of neonatal sepsis are based largely on cases that reach the hospital, which undoubtedly underestimates the incidence in the community. In pooled data from hospital-based case series, the incidence was 6 cases per 1000 live births (Stoll, 2000); other studies suggest that rates may be even higher (Kuruvilla et al., 1998; Asindi et al., 1999). Among patients enrolled in the WHO Young Infants Study—a study of infants under 3 months of age with serious infections conducted at four sites (Ethiopia, the Gambia, Papua New Guinea, and the Philippines)—30 percent of infants with a positive blood culture died (WHO Young

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
×

Infants Study Group, 1999a). In 47 hospital-based studies, case fatality rates were as high as 69 percent (Stoll, 2000). Left untreated, bloodstream infections can spread to the meninges, resulting in meningitis. Estimates of neonatal meningitis incidence range from 0.3 to 2.8 per 1,000 live births (average 1/1000 live births), and reported case fatality rates range from 13 to 59 percent (Stoll, 2000).

Omphalitis (umbilical infection) continues to be a problem in developing countries (Cushing, 1985). Births in the home, nonsterile cutting of the cord, and unhygienic cord care after birth all increase the risk of omphalitis. Because localized umbilical infection is not prevented and may be inadequately treated in developing-country settings, it may be associated with the subsequent development of necrotizing fasciitis and/or neonatal sepsis (Faridi et al., 1993; Weber et al., 2001). Moreover, omphalitis in patients with neonatal tetanus (discussed below) is associated with an increased risk of bacterial sepsis (Egri-Okwaji, 1998).

Because the majority of developing-country studies that present data on the bacterial etiology of neonatal sepsis and meningitis are hospital-based, they may not reflect what is happening at the community level. While group B streptococcus (GBS) remains an important cause of early neonatal sepsis in industrialized countries (Schuchat, 1998), it appears to be a much less important pathogen in developing countries (WHO Young Infants Study Group, 1999a; Stoll, 2000). The most frequent organisms reported from case series in developing countries are gram-negative organisms (especially Escherichia coli and Klebsiella) and Staphylococcus aureus (Stoll, 2000; Mulholland, 1998). The organisms responsible for neonatal sepsis and meningitis are similar, change over time, and vary by geographic region. Therefore, prospective microbiological surveillance is key for prevention and appropriate treatment of these diseases.

The emergence of antibiotic-resistant pathogens is a particularly alarming problem in developing countries. Hospital-based studies of the bacterial etiology of neonatal sepsis and reports of nosocomial outbreaks from a variety of countries demonstrate that the problem of antibiotic resistance is of global concern (Banerjee et al., 1993; Reish et al., 1993; Haddad et al., 1993; Bhutta, 1996; Ako-Nai et al., 1999; Musoke, 1997; Musoke and Revathi, 2000). The widespread availability of antibiotics and their indiscriminate and inappropriate use contribute to this problem, along with poor infection-control practices in hospitals.

Surveillance capacity and the transfer of surveillance information must be developed to determine both the global and local impact of resistant microorganisms and to identify interventions that can address this threat (Williams, 2001). Strategies are needed to reduce the risk of infection, as well as to encourage the judicious prescription and appropriate use of antibiotics in the community and in hospital (Levy, 2001; Boyce, 2001;

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
×

Perchère, 2001; Bell, 2001; de Man et al., 2000). Some epidemiologists caution, however, that the prudent use of antibiotics is unlikely to reverse resistance trends and that the true clinical impact of antibiotic resistance has not yet been measured (Phillips, 2001).

Acute respiratory infections

Pneumonia and other acute respiratory infections (ARIs) account for up to a quarter (Pan American Health Organization, 1999) or perhaps more of all mortality in children under 5, but it is difficult to determine the incidence of neonatal ARI in developing countries because many sick neonates are not referred for medical care. The risk of death due to ARI is highest in young neonates and decreases with age (Garenne et al., 1992).

Most ARI deaths are due to pneumonia, which annually kills more than 3 million children under the age of 5 in developing countries (Garenne et al., 1992). Like sepsis, neonatal pneumonia may have an early onset if acquired from the maternal genital tract or a late onset due to infection from the hospital or home environment. Bacterial pneumonia is the most common; streptococcus pneumoniae is the most frequent cause. Low birth weight is associated with higher mortality (Misra et al., 1991). The risk of pneumonia increases in infants who are of low birth weight and/or malnourished, and in those who are not breastfed (Victora et al., 1999).

In preterm neonates of low birth weight, respiratory distress syndrome, due to surfactant deficiency, is a major risk for early death (Mlay and Manji, 2000). Information on the prevalence of this disorder in developing countries is especially difficult to obtain because most infants of very low birth weight (those weighing less than 1500 grams, who are at greatest risk) die soon after birth. In these cases, causes of death other than prematurity are poorly recognized (Bhutta et al., 1999).

Tuberculosis

A leading infectious disease, tuberculosis (TB) kills more than 2 million people worldwide each year, including 250,000 children, despite the availability of cost-effective prevention and treatment (United Nations Children’s Fund, 2000). The vast majority of these deaths occur in developing countries; approximately 70 percent of all TB cases occur in Asia (United Nations Children’s Fund, 2000). TB is a particular risk in areas where HIV is prevalent, as approximately 40 percent of people whose immune systems have been weakened by HIV develop TB (United Nations Children’s Fund, 2000; Thillagavathie, 2000). The reportedly higher TB prevalence in men than in women appears to be an artifact of gender differences in notification rates (Thorson and Diwan, 2001).

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
×

In pregnant women, TB has been shown to increase the risk of fetal loss, preterm delivery, and low birth weight (Starke, 1997; Jana et al., 1994). Although rare, transplacental congenital infection may occur (Connelly Smith, 2002; Starke, 1997); infection with HIV increases a woman’s risk for placental or genital TB. The most common route of mother-to-child transmission is postnatal from an untreated infected mother to her newborn. Infected newborns are at high risk for severe disseminated TB and death (Starke, 1997; Adhikari et al., 1997).

Diarrheal disease

Several community-based studies suggest that diarrhea is responsible for approximately 3 percent of all neonatal deaths (Stoll, 2000). Diarrheal episodes tend to occur with greatest frequency among children aged 6 months to 2 years; in many developing countries, initial episodes frequently occur in the first 6 months of life (Bern et al., 1992; Snyder and Merson, 1982; Jacobson, 1999). Some factors common to developing countries—home delivery; relative segregation of newborn infants for a period of time after birth; and the high prevalence of early, exclusive breastfeeding—protect against neonatal diarrhea. Among hospitalized newborns in developing countries, nosocomial diarrhea is an important problem (Aye et al., 1991; Yankauer, 1991; Tessema, 1994).

Rotavirus

Rotavirus is an important cause of diarrhea among infants and children worldwide, occurring most commonly in those aged 3 months to 2 years. However, several studies from developing countries report rotavirus infections in newborns (Haffejee, 1995; Parashar et al., 1998b; Cicirello et al., 1994; Espinoza et al., 1997; Gomwalk et al., 1990).

Tetanus

Worldwide, about a quarter-million infants die from tetanus each year (Table 3-1). Risk factors for neonatal tetanus occur in the antenatal, perinatal, and neonatal periods: failure to immunize the mother against tetanus; unhygienic delivery and cutting of the umbilical cord at birth; and unsterile handling of the cord in the early days of life. Cultural practices prevalent in specific areas, such as the application of ghee (Pakistan and India) and other unclean substances to the cord after birth increase risk (Traverso et al., 1991). Diagnosis of neonatal tetanus is relatively straightforward: the newborn can suck at birth and for the first few days of life, then loses this ability between 3 and 10 days of age, then develops spasms, stiffness,

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
×

convulsions, and death. For decades, community surveys have determined the burden of disease and mortality rates for tetanus (Galazka and Stroh, 1986). Routine national surveillance, however, may still underestimate the true occurrence of the disease (Singh et al., 1997). In some of the least-developed countries, neonatal tetanus remains a major cause of neonatal death, particularly among infants delivered at home and without skilled assistance (Gasse, 1995; Gupta and Keyl, 1998; Gurkan et al., 1999; Davies-Adetugbo et al., 1998).

Between 1990 and 2000, deaths caused by neonatal tetanus declined by half through a combination of maternal immunization and clean delivery practices (United Nations Children’s Fund, 2002). Substantial reductions in neonatal mortality due to tetanus occurred in China, Indonesia, Bangladesh, India, and Pakistan. Nevertheless, approximately 250,000 neonates died of tetanus during 1997; the majority of these deaths occurred in Africa and Southeast Asia, with nearly 20 percent in India (World Health Organization, 1999a).

Sexually transmitted diseases

More than 333 million cases of the four major curable STDs—syphilis, gonorrhea, chlamydia, and trichomoniasis—were estimated to occur in 1995, the vast majority in developing countries (Gerbase et al., 1998). Collectively, STDs rank among the leading causes of morbidity worldwide, a burden borne disproportionately by women of reproductive age. STDs among pregnant women often receive delayed treatment or none at all, largely because they are asymptomatic or unrecognized (Sturm et al., 1998). Most STDs are readily transmitted from mother to child during pregnancy and/or childbirth (Moodley and Sturm, 2000). The extent of neonatal infections with these agents in developing countries is difficult to estimate. Adverse pregnancy outcomes associated with STDs range from miscarriage and preterm birth (see Chapter 7) to congenital infections to maternal, fetal, and neonatal mortality (Carroli et al., 2001a; Moodley and Sturm, 2000). Neonatal HIV is discussed in detail in Chapter 8.

Among women worldwide, there are approximately 7 million new cases of syphilis each year (Gerbase et al., 1998). Rates of congenital syphilis parallel those of syphilis in women of reproductive age. Many developing-country studies have found seroprevalence rates of syphilis among pregnant women of 5 to 15 percent, or up to two orders of magnitude higher than typical rates in developed countries (Carroli et al., 2001a); in South Africa, rates of infection in pregnant women have been reported to range from 6 to 19 percent (Rotchford et al., 2000). Untreated syphilis during pregnancy increases the risk of late fetal death, low birth weight, preterm birth, and severe neonatal disease (Lumbiganon et al., 2002). Data from a demonstra-

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
×

tion project in Zambia determined that syphilis was the most significant cause of adverse pregnancy outcome among women attending antenatal clinics (Hira et al., 1990); a more recent prospective study of congenital syphilis in a Papua New Guinea hospital found that the infection was responsible for 6 percent of admissions and 22 percent of all neonatal deaths (Frank and Duke, 2000).

Syphilis is transmitted from an infected mother to the fetus largely via transplacental infection, and rarely via contact with an infectious genital lesion during delivery. Active infection with syphilis in pregnant women is estimated to result in fetal or infant death or disability for 50 to 80 percent of affected pregnancies (Gloyd et al., 2001). The majority of infants born to mothers with untreated syphilis are asymptomatic at birth, but if left untreated may develop clinical manifestations of disease months to years after birth (Dorfman and Glaser, 1990; Sanchez et al., 1991). Symptoms of early congenital syphilis include intrauterine growth restriction, anemia, thrombocytopenia, jaundice, and hepatosplenomegaly (Stoll et al., 1993). The most devastating complications of untreated or late congenital syphilis are neurological manifestations that include mental retardation, hydrocephalus, cranial nerve palsies, and seizures (Stoll, 1994). With adequate treatment of infected mothers, syphilis is a preventable cause of neonatal morbidity and mortality.

Neonates delivered vaginally to mothers with untreated gonorrhea are at great risk of developing gonococcal conjunctivitis, which, if left untreated, can lead to blindness. Rarely, neonates develop disseminated gonococcal infection (Desenclos et al., 1992; Rawstron et al., 1993). Similarly, chlamydia infections occur in approximately two-thirds of infants born by vaginal delivery to infected mothers (Moodley and Sturm, 2000). Chlamydia can cause conjunctivitis and/or pneumonia, which may not be evident until the infant is several weeks old.

Neonatal infection with herpes simplex usually occurs during delivery, via an infected birth canal or an ascending infection following the rupture of membranes to women with primary genital herpes at the time of delivery (Prober et al., 1988; Brown et al., 1996; Brown et al., 1987). The infection can spread to the central nervous system and beyond, and has both a high mortality rate and a high likelihood of neurodevelopmental sequelae among survivors (Tookey and Peckham, 1996; Brkic and Jovanovic, 1998; Jacobs, 1998; Whitley et al., 1991).

Maternal urinary tract infections

Infections of the urinary tract, particularly asymptomatic bacteriuria, occur in an estimated 4 to 7 percent of all women (Carroli et al., 2001a; Dempsey et al., 1992;). Unless the infection is treated with antibiotics, an

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
×

estimated 20 to 40 percent of pregnant women with asymptomatic bacteriuria will develop pyelonephronitis (Smaill, 2003); of those who do, 20 to 50 percent will experience preterm deliveries (Carroli et al., 2001a). Antibiotic treatment is associated with reductions in preterm delivery and low birth weight (Smaill, 2003).

Malaria

Malaria in pregnancy has serious health consequences for both mother and newborn. Because it causes significant maternal morbidity, its prevention and treatment are discussed in Chapter 2. The primary malaria-associated risk for neonates is reduced birth weight, which is discussed in Chapter 6. In highly endemic settings, malaria has been estimated to account for 13 percent of low birth weight (LBW) due to intrauterine growth restriction (IUGR) (Steketee et al., 1996).

Noninfectious Conditions
Perinatal asphyxia

Of the estimated 4 to 7 million neonates born each year worldwide that require some form of resuscitation immediately after birth, approximately 1 million die and another million suffer serious sequelae (Saugstad et al., 1998). Epidemiological data provide only rough estimates of the global burden of perinatal asphyxia, in part because of the imprecision of diagnosis. Numerous definitions of perinatal asphyxia, all of which correspond to the failure to initiate and sustain normal breathing, have been used in studies from developing countries. These include apnea or gasping with a slow heart rate (<80) at birth, absent or poor respiratory effort at 1 minute, gasping at 1 minute, low Apgar scores (variously defined), and the need for assisted ventilation for more than 1 minute (Paul et al., 1997; Chandra et al., 1997; Daga et al., 1990; Saugstad et al., 1998; Kinoti, 1993). In addition, data on perinatal asphyxia are largely hospital-based and therefore may either underestimate or overestimate the true magnitude of the problem, as seen in many studies (Paul et al., 1997; Chandra et al., 1997; Daga et al., 1990; Kinoti, 1993; Chaturvedi and Shah, 1991; Boo and Lye, 1991; Nathoo et al., 1990; Ellis et al., 2000).

The incidence of perinatal asphyxia is thought to be higher in developing than developed countries because of the higher prevalence of risk factors for the disorder, as well as the lack of appropriate interventions (Deorari et al., 2000). Mortality is greater among preterm than term infants, and decreases with increasing birth weight. However, asphyxia also has an important effect on mortality among normal-weight term in-

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
×

fants, who otherwise have a good chance for survival (Paul et al., 1997). The contribution of perinatal asphyxia to long-term neurodevelopmental disability in developing countries is unclear (Ellis et al., 1999).

Conditions that increase the risk of asphyxia include antepartum hemorrhage, prolonged labor and/or prolonged rupture of membranes, drugs given to the mother that may depress respiration (e.g., magnesium sulfate, narcotics), cord accidents, vaginal breech deliveries, multiple gestation, pregnancy-induced hypertension, congenital anomalies, and IUGR with placental dysfunction (Chandra et al., 1997; Daga et al., 1990; Chaturvedi and Shah, 1991; Boo and Lye, 1991; Nathoo et al., 1990). In most resource-poor countries, where the vast majority of births take place at home, asphyxia is difficult to anticipate. The passage of meconium in the amniotic fluid and an abnormal fetal heart rate (bradycardia or persistent tachycardia) are the only simple ways to predict asphyxia prior to delivery in most developing countries; only about half of all cases can be detected this way (Chaturvedi and Shah, 1991).

Birth injury

Birth injury is a nonspecific term that includes potentially preventable and unavoidable injuries—mechanical or hypoxic-ischemic—suffered by the neonate during labor and delivery. Specific injuries include intracranial hemorrhage; blunt trauma to the liver, spleen, or other internal organs; injury to the spinal cord or peripheral nerves (the most devastating is cord transection; the most common is brachial plexus injury); and fractures to the clavicles or extremities.

Although WHO has estimated that birth injuries are responsible for 11 percent of neonatal deaths worldwide (World Health Organization, 1996c), the incidence of specific injuries in most developing countries is unknown. Birth injuries can result in transient neonatal problems, long-term morbidity, and death. Predisposing factors include macrosomia, cephalopelvic disproportion, dystocia, prolonged or obstructed labor, breech presentation, and prematurity. Although injury may occur despite skilled care at delivery, some injuries result from inadequate medical knowledge or suboptimal care during labor and delivery and are therefore potentially preventable. A specific diagnosis is preferable to the use of the nonspecific term “birth injury,” especially when considering prevention strategies.

Hypothermia

Hypothermia, defined as a body temperature below 36.5°C, is frequent in newborns, especially those of low birth weight. Several studies have shown that without adequate care, many newborns will experience severe

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
×

hypothermia, reaching core temperatures lower than 32°C (Ellis et al., 1996). Neonatal hypothermia has been reported to increase the risk of infection, coagulation abnormalities, acidosis, complications of preterm birth, and death (Dragovich et al., 1997; Dagan and Gorodischer, 1984; Manzar, 1999).

Dragovitch et al. (1997) evaluated the knowledge and practices of health professionals on thermal control of newborns in seven countries: Brazil, India, Indonesia, Kazakhstan, Mozambique, Nepal, and Zimbabwe. They found that thermal control practices were frequently lacking in the following areas: ensuring a warm environment at the time of delivery, initiation of breastfeeding and contact with the mother, bathing, checking the baby’s temperature, thermal protection of low-birth-weight neonates, and care during transport. The study also demonstrated that health professionals involved in newborn care underestimate the impact of hypothermia on neonatal morbidity and mortality. A recent survey of health professionals involved in newborn care in an Indian hospital revealed similarly weak knowledge of hypothermia diagnosis and care; for example, fewer than one-fifth of the respondents knew the correct method of measuring the body temperature of a newborn (Choudhary et al., 2000).

Neonatal jaundice/hyperbilirubinemia

Since most births occur at home, the magnitude of this problem is unknown. Although a relatively rare cause of death in neonates, untreated extreme bilirubinemia can cause devastating neurologic injury, long-term disability or death. With adequate vigilance, detection, and treatment such infrequent but severe damage can be prevented. The major risk of untreated hyperbilirubinemia is bilirubin encephalopathy or kernicterus (Dennery et al., 2001; Alpay et al., 2000). In the first week of life, visible jaundice occurs in approximately 15 percent of newborns (Cashore, 1994). However, many more with elevated bilirubin below 7 to 8 mg/dL do not develop jaundice and the bilirubin elevation remains undetected. However, mild elevation, though common, need not cause harm to the baby. Causes of hyperbilirubinemia include prematurity, blood group incompatibility, and peripartum infection. Most often, elevated levels of bilirubin in the baby’s blood come about from breakdown of hemoglobin in old or hemolyzed red blood cells (Dennery et al., 2001). There are many causes of indirect hyperbilirubinemia, including increased production of bilirubin, impaired conjugation, and increased enterohepatic circulation. The reason for racial differences in hyperbilirubinemia has some genetic basis but is not completely understood (Setia et al., 2002; Dennery et al., 2001; Akaba et al., 1998). The risk of Rh hemolytic disease has been markedly reduced in industrialized countries by the use of Rh immune globulin (Rhogam)

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
×

(Queenan, 2002). However, Rh disease remains a problem in developing countries, where most women deliver at home, blood type is unknown, and Rhogam is not available.

Kernicterus or bilirubin encephalopathy results from deposition of unconjugated bilirubin in the basal ganglia. Kernicterus is rare in healthy term infants in the absence of hemolysis if the serum bilirubin level is under 25 mg/dL (Gourley, 1997; Hansen and Bratlid, 1986). The duration of exposure required for toxicity is unclear. Preterm infants are at greater risk for kernicterus, but the exact level at which toxicity occurs is unknown. The early signs of bilirubin encephalopathy are nonspecific (lethargy, poor feeding), but the infant may become critically ill with bulging fontanel, opisthotonus, shrill cry, spasms, and seizures. Late sequelae of kernicterus include extrapyramidal abnormalities, choreoathetosis, involuntary muscle spasms, and sensorineural deafness.

INTERVENTIONS

Reducing neonatal mortality and morbidity often involves established interventions or strategies along with the means to make them effective in each setting. For many conditions, improved education and behavioral change among women, families, and health care providers would have a major impact on birth outcomes. For direct impact, emphasis must be given to the delivery of care: getting appropriate services to those who need them and doing so in a timely manner. Interventions to reduce neonatal mortality and morbidity are discussed below, with emphasis on antenatal care, care during labor and delivery, and care during the early days and weeks of life.

Antenatal Care

Medical factors that may contribute to neonatal morbidity and mortality include several components that can be directly addressed by antenatal care: poor maternal health and nutrition, maternal infections, and lack of immunization against tetanus (Villar et al., 2001; Carroli et al., 2001a, 2001b; Bergsjo and Villar, 1997). Equally important, as described in the previous chapter, antenatal care can teach mothers to recognize signs during pregnancy, labor, and delivery and encourage them to plan clean and safe deliveries—preferably with trained assistance (Bloom et al., 1999). Appropriate antenatal care also includes explaining the benefits of breastfeeding, childhood immunization, and personal and domestic hygiene, and teaching parents to recognize danger signs that can occur in newborns.

As noted in the introduction to this report, maternal education has a

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
×

significant and far-reaching impact on antenatal care (Bicego and Boerma, 1993; Victora et al., 1992; Terra de Souza et al., 2000; van Ginneken et al., 1996; Rao et al., 1996). Better formal and health education of girls leads them in later years to seek preventive services, increase food intake during pregnancy, reduce tobacco and alcohol use, understand the implications of danger signs during labor and delivery, and seek referral care for obstetric and/or newborn complications (World Bank, 1993; Ahmed et al., 2001).

The discussion in this chapter focuses on those antenatal interventions that are directed at preventing and treating maternal conditions that directly affect the neonate. Antenatal care directed at maternal morbidity and mortality is discussed in Chapter 2, at low birth weight in Chapter 6, at birth defects in Chapter 7, and at mother to infant transmission of HIV in Chapter 8. Findings from these chapters are assembled in a list of essential antenatal care interventions in the executive summary and the concluding chapter (9).

Diagnosis and treatment of maternal infections

Timely diagnosis and treatment of maternal infections and other health problems during pregnancy can lead to significant improvement in fetal and neonatal outcomes, as well as prevention of maternal mortality and morbidity. These are discussed in Chapter 2. Conditions of particular concern to the neonate include the following:

Sexually transmitted diseases. Treatment of STDs is cost-effective (Mayaud et al., 1995), but clinical diagnosis is difficult because the symptoms are not specific, laboratory support is often unavailable (Bosu, 1999), and simple, inexpensive, sensitive tests exist only for syphilis (Moodley and Sturm, 2000). For these reasons, WHO has recommended a syndromic approach to diagnosing and treating STDs in low-resource settings (World Health Organization, 1994). However, the efficacy of syndromic treatment, especially among pregnant women, is unclear (Mayaud et al., 1995, 1998; Sturm et al., 1998). Several studies have documented that STDs facilitate HIV transmission (Fleming and Wasserheit 1999). A randomized, controlled trial in the Mwanza region of Tanzania concluded that STD treatment significantly reduced the incidence of HIV infection (Grosskurth et al., 1995) and was highly cost-effective (Gilson et al., 1997). A community-based, randomized trial of STD control in the Rakai district of Uganda (where the HIV infection rate is higher) demonstrated that reduction of STDs improved pregnancy outcome (reduced the rate of low birth weight, infant ophthalmia, and early neonatal mortality), but did not reduce transmission of HIV to mother, fetus, or neonate (Gray et al., 2001). All women were treated for syphilis if their serological test was positive. Other STDs were treated presumptively in randomized fashion using antibiotics effec-

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
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tive against a wide range of pathogens. Further research is needed to determine the optimal strategy to reduce the neonatal impact of STDs in developing countries. Two possibilities are presumptive therapy for all pregnant women and development of cost-effective diagnostic tests for use in field settings to facilitate prompt maternal therapy.

Serologic screening of pregnant women for syphilis has been shown cost-effective even in areas where disease prevalence is low (Carroli et al., 2001a; Gloyd et al., 2001; Frank and Duke, 2000; Schmid, 1996). WHO recommends universal antenatal screening for syphilis; in areas of high prevalence of the disease, screening should be performed at the first antenatal visit and repeated early in the third trimester (Lumbiganon et al., 2002). Treatment in the last trimester of pregnancy may not ensure that the fetus/ newborn is uninfected at birth. If adequate maternal treatment cannot be documented, the infant should be treated for syphilis.

Rapid, inexpensive serological tests for syphilis increase the likelihood a woman will receive adequate treatment by allowing her to be screened and treated in the same clinic visit (Rotchford et al., 2000; Wilkinson and Sach, 1998). Routine screening is less effective as it involves follow-up of both the mother and her sexual partner(s). A “second-best” strategy in areas of low syphilis prevalence is the screening of high-risk groups, then examination of women with symptoms and those whose partners report symptoms (Carroli et al., 2001a).

Routine screening for chlamydia during pregnancy has not proven cost-effective (Carroli et al., 2001a). WHO recommends that maternal screening and antibiotic treatment be considered in populations where chlamydia prevalence in pregnant women exceeds 10 percent and where some infants with chlamydial pneumonia are hospitalized at high cost. Sexual partners must also be treated to prevent reinfection during pregnancy (World Health Organization, 1996a).

In areas where HIV testing and counseling are readily available, WHO recommends that those services be offered to pregnant women, especially those at high risk for HIV infection (World Health Organization, 1996a). Chapter 8 examines the role of antenatal care in prevention of mother-to-infant transmission of HIV.

Urinary tract infection. Evidence from several randomized controlled trials indicates that antibiotic treatment of urinary tract infection and/or asymptomatic bacteriuria reduces the risk of low birth weight, but the mode of prevention is unclear. Screening for and treatment of asymtomatic bacteriuria during pregancy are recommended in order to prevent maternal pyelonephritis, as well as reduce risk to the neonate (Smaill, 2003).

Tuberculosis. Policies for screening pregnant women for TB, a leading cause of death in some parts of the world, may be adapted to local epidemiology and TB control programs (Ahmed et al., 1999). Some experts believe

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
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that only women with specific risk factors for tuberculosis infection or disease should receive a tuberculin skin test as part of antenatal care. Women coinfected with tuberculosis and HIV are at particularly high risk (Pillay et al., 2001). Women with positive skin tests require a chest radiograph to rule out active pulmonary disease and are referred for therapy if the radiograph is abnormal. Treatment of tuberculosis during pregnancy is essential (Pillay et al., 2001); the specific drugs provided depend on safety and efficacy in pregnancy (Starke, 1997), as well as local patterns of drug sensitivity (Davidson, 1995).

Malaria prevention and treatment in pregnant women is discussed in Chapter 2.

Rubella infection during pregnancy (especially the first trimester) can result in miscarriage, late fetal death, or congenital rubella syndrome. Congenital rubella syndrome and possibilities for prevention are discussed in Chapter 7. Immunization of school children and preconceptional women is recommended in countries as long as immunization reaches more than 80 percent of the population.

Maternal immunization

Fetuses, neonates, and young infants can be protected from a variety of infections through passively acquired transplacental and breast milk antibodies. For example, antenatal immunization against rubella provides low-cost, effective protection from congenital rubella syndrome. Because most IgG antibody is transported across the placenta in the last 4–6 weeks of pregnancy, maternal immunization to protect the infant is most promising for term babies. For preterm infants there is insufficient passage of maternal antibodies. However, boosting breast milk antibodies by immunizing mothers can protect both term and preterm infants.

Tetanus. Immunization of pregnant women with tetanus toxoid, which has dramatically reduced cases of neonatal tetanus, is an important, low-cost antenatal intervention (Gupta and Keyl, 1998; Jeena et al., 1997; Bergsjo and Villar, 1997. Moreover, maternal tetanus immunization has been associated not only with lower neonatal mortality but also with lower early childhood mortality (Luther, 1998). In a study in Bolivia, traditional birth attendants employed single-use, prefilled injection devices to immunize more than 2,000 pregnant women against tetanus during routine antenatal visits. Because tetanus toxoid is relatively heat-stable, the prefilled devices could be stored for up to one month without refrigeration (Quiroga et al., 1998). A study in Bangladesh showed that tetanus toxoid immunization rates were positively associated with proximity to outreach clinics and the presence of a health worker in community and home visits. The effects were greatest in poorer households (Jamil et al., 1999).

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
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Pneumonia. Maternal vaccines have been developed to protect neonates and infants against Streptococcus pneumoniae, Haemophilus influenzae type B, and Group B streptococcal infections (Child Health Research Project Special Report, 1999; Glezen and Alpers, 1999; Mulholland et al., 1996; Mulholland, 1998; Monto and Lehman, 1998). Studies in Bangladesh and Papua New Guinea showed that maternal immunization with pneumococcal polysaccharide vaccines produced an increase in type-specific serum IgG antibody level in both mother and newborn (Shahid et al., 1995; Lehmann et al., 2002). Combination vaccines would be especially useful for populations with limited access to health services (Monto and Lehman, 1998).

H. influenzae type B. In developed countries, invasive disease resulting from H. influenzae type B (HiB) has been almost eliminated by the use of HiB conjugate vaccines (Bisgard et al., 1998). In many countries, however, HiB remains an important cause of life-threatening infections in infancy, particularly pneumonia and meningitis. Maternal immunization with HiB polysaccharide-tetanus protein conjugate vaccine has been shown to increase both maternal and neonatal antibody concentrations: at 2 months of age, 60 percent of the infants of vaccinated mothers had protective levels of antibody (Mulholland et al., 1996).

Before routine maternal immunization with these vaccines can be recommended, further studies are needed to determine each vaccine’s short-and long-term safety for the fetus and newborn, and its efficacy in preventing neonatal disease. Moreover, the delivery of vaccines to those who need them in poor countries is a massive task that will necessitate novel public-private partnerships (Smith, 2000).

Prevention and treatment of anemia

In developing countries, anemia has several possible causes, including iron or other micronutrient deficiencies, malaria, and hookworm (van den Broek and Letsky, 2000). Antenatal iron supplementation and prevention and treatment of the salient infections are discussed in Chapters 2 and 6.

Recognition and reversal of breech presentation

Late in pregnancy, abdominal examination can reveal a fetus in breech presentation, a significant risk factor for obstructed labor. To reduce the attendant risk to the fetus and newborn of intrapartum or postpartum asphyxia or birth injuries, external cephalic version may be attempted after 37 weeks’ gestation (Villar and Bergsjo, 1997).

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
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Essential antenatal care

Evidence from several randomized trials indicates that similar maternal and neonatal outcomes could be obtained from antenatal care in as few as five visits (on average) by focusing on interventions known to be effective in reducing morbidity and mortality (Villar et al., 2001; Carroli et al., 2001b): counseling on birth preparedness and emergency readiness; provision of folic acid; tetanus immunization; prophylaxis and intermittent preventive treatment for malaria and hookworm as needed; and early detection and timely management of certain diseases or complications (severe anemia at the end of pregnancy, hypertension and proteinuria, asymptomatic bacteriuria and urinary tract infection, syphilis, HIV, and other sexually transmitted diseases prevalent in the local population, and concurrent conditions such as hepatitis, malaria, and tuberculosis); and fetal malpresentation after the 37th week. A multicenter randomized, controlled trial conducted in more than 50 clinics in Argentina, Cuba, Saudi Arabia, and Thailand concluded that women assigned to the new model of essential antenatal care that called for an average of five visits per pregnancy had similar rates of low birth weight, postpartum anemia, urinary tract infection, and several secondary outcomes to those of women enrolled in a standard antenatal care program with an average of eight visits (Villar et al., 2001). This finding is further supported by a systematic review of seven randomized controlled trials that assessed the effectiveness of different antenatal care models in reducing adverse outcomes for mother and infant (Carroli et al., 2001b).

Care During Labor, Delivery, and the Very Early Neonatal Period

Complications of pregnancy and childbirth, a leading cause of death and disability among women of reproductive age (see Chapter 2), can also cause neonatal illness and death. Every pregnancy is at risk for complications, most of which can be managed successfully if recognized and addressed in a timely manner. However, the fact that the majority of births in developing countries occur outside hospitals and other health care facilities presents special challenges.

One such challenge is the use of poor aseptic techniques during labor and delivery, which lead to maternal and neonatal infections. The birth attendant can play a critical role in preventing infections of the mother and newborn by observing the need for clean hands, clean perineum, clean delivery surface, clean instruments, clean cord care, and use of an appropriate clean delivery kit.

The goal is for every delivery to be assisted by a skilled birth attendant such as a midwife, physician, or nurse (as described in Chapter 2). As well

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
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as providing a clean and safe delivery, a trained birth attendant recognizes complications such as preterm birth, preterm or prolonged rupture of membranes, and prolonged or obstructed labor and can promptly refer the patient to a health facility with essential obstetric and neonatal care. Skilled interventions are key for saving neonatal and maternal lives during labor, delivery, and the very early neonatal period.

Prevention and treatment of neonatal infections

Neonatal sepsis and pneumonia. Preterm or prolonged rupture of the membranes, maternal fever during labor, and chorioamnionitis are risk factors for early-onset neonatal sepsis and pneumonia. Because the risk of infection increases with the number of vaginal examinations performed during labor, the number of examinations should be minimized (Seaward et al., 1997). Induction of labor in pregnancies at term with prelabor rupture of membranes or chorioamnionitis can prevent infection of both mother and newborn (Tan and Hannah, 2001). In industrialized countries, intrapartum antibiotics are used to reduce both maternal and neonatal sepsis (Gibbs et al., 1988; Benitz et al., 1999): broad-spectrum antibiotics for women suspected to have chorioamnionitis to reduce maternal and neonatal infection (Gibbs et al., 1988); antibiotics for mothers with preterm rupture of membranes to reduce neonatal illness (Mercer et al., 1998); and intrapartum penicillin to prevent mother to neonate transmission of group B streptococcal infection (Schuchat, 1998). Some of these interventions may be adaptable to community-level use in developing countries.

When a mother develops a puerperal infection, the newborn requires special attention and should be treated for presumed sepsis. Ideally, infants at risk for sepsis who are born at home should be referred to the nearest health facility for observation and antibiotic treatment. Where this is not possible, ways to deliver care to the mother and newborn in the home need to be developed and evaluated (see Box 3-1 below).

Cord infections. Use of a sterile blade to cut the cord and a clean tie are essential. Clean cord care in the postnatal period includes washing hands before and after care and keeping the cord dry and exposed to air or loosely covered with clean cloths. The application of antimicrobial or antiseptic agents to the cord after birth reduces bacterial colonization of the cord and is a routine practice in many industrialized countries. In developing countries, where bacterial contamination of the cord is a higher risk, local antimicrobial agents might reduce infection. A small study in Papua New Guinea documented a decrease in neonatal sepsis following a simple cord care intervention: cutting the cord with a new razor blade and applying acriflavine spirit (Garner et al., 1994). Further studies are warranted.

Neonatal tetanus. Neonatal tetanus can be prevented by immunizing

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
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women before or during pregnancy and by ensuring a clean delivery, clean cutting of the umbilical cord, and proper care of the cord in the days following birth (Gupta and Keyl, 1998; Parashar et al., 1998a). Although tetanus toxoid is a highly effective immunogen (Gupta and Keyl, 1998; Koenig et al., 1998; McCarroll et al., 1962), cases of neonatal tetanus have been reported in infants born to fully immunized mothers (Hlady et al., 1992; Talukdar et al., 1994; de Moraes-Pinto et al., 1995; Davies-Adetigbo et al., 1998). These outcomes highlight the need for quality control of tetanus vaccine production and promotion of hygienic cord care practices. The protective efficacy of topical antimicrobials has been demonstrated by several case-control studies (Traverso et al., 1991; Bennett et al., 1997; Parashar et al., 1998a). The use of topical antimicrobials as a complement to maternal immunization warrants further study as part of the global effort to eliminate this disease.

Sexually transmitted diseases. Additional intrapartum or immediate postpartum interventions for infants born to mothers with confirmed or suspected STDs can prevent neonatal morbidity. WHO recommends that until syphilis screening and treatment in pregnancy have been fully and effectively implemented, all infants born to seroreactive mothers be treated for syphilis infection (World Health Organization, 2001). Prevention of mother-to-child transmission of HIV is discussed in Chapter 8.

Gonococcal ophthalmia neonatorum is prevented by antimicrobial eye prophylaxis immediately after birth. The cheapest and most widely available agent is silver nitrate (1 percent) eye drops; however, old, more concentrated solutions have been implicated in causing chemical conjunctivitis (Moodley and Sturm, 2000; World Health Organization, 1991). Topical erythromycin and tetracycline are more expensive but safer drugs for prevention of gonococcal ophthalmia (Laga et al., 1988); given increasing tetracycline resistance, erythromycin is the preferred choice (Moodley and Sturm, 2000).

In areas where genital herpes is the predominant cause of genital ulcer disease, WHO recommends cesarean delivery when herpetic lesions are present in the genital tract at the time of membrane rupture or during labor, if the patient presents within 4-6 hours of labor’s onset, and if the risk for morbidity and mortality due to surgery or anesthesia are low. If genital herpes is a relatively minor cause of genital ulcer disease—that is, where chancroid and syphilis predominate—cesarean section is contraindicated since the predictive value of genital ulcers for HSV is low, and surgery-related morbidity may be high (Anonymous, 2000; Roberts et al., 1995).

Care of noninfectious conditions

Resuscitation. Skilled birth attendants should be proficient in neonatal resuscitation and ready to perform it at every birth, since asphyxia is usu-

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
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ally unpredictable. The basic resuscitation procedure involves having appropriate equipment available (tube/mask or bag/mask); being prepared for and anticipating potential problems; using a warm, clean, flat surface; drying, stimulating, and assessing the newborn; clearing the airway, and ventilating a newborn who fails to initiate respiration. Complex interventions, such as endotracheal intubation, chest compression, and medications, are rarely needed. Use of a simple bag and mask to ventilate the newborn is the established practice in industrialized countries, and has been successfully adapted to low resource settings (Palme-Kilander, 1992; Deorari et al., 2000; Alisjahbana et al., 1999). Preliminary studies indicate that a simple mouth-to-mask (tube and mask) device is as effective as a bag and mask in the resuscitation of asphyxiated newborns (Milner et al., 1990; Massawe et al., 1996). Furthermore, a recent multinational trial demonstrated that neonates can be resuscitated with room air as efficiently as with oxygen (Saugstad et al., 1998). This is particularly important for home deliveries where supplemental oxygen is not available (Saugstad et al., 1998; Saugstad, 1998). The nearly 1 million births annually that are complicated by asphyxia could be improved through management of labor and childbirth that reduces the risk of asphyxia, and prompt resuscitation of newborns who fail to breathe at delivery.

Thermal control. Optimal thermal control of newborn infants in developing countries can be promoted by ensuring a warm environment for delivery in the home or hospital, drying the infant soon after birth, providing clean, dry clothing and blankets for mother and newborn, and keeping all newborns—including preterm infants—with the mother soon after birth. Maintaining skin-to-skin contact between mother and newborn efficiently stabilizes temperature in term infants and permits the early establishment of breastfeeding. Continuing skin-to-skin contact (Kangaroo care), proposed in 1978 by Rey and Martinez (Simkiss, 1999) is even more important for low-birth-weight and preterm infants. In the Kangaroo care method, a well low-birth-weight infant, wearing only a diaper, is placed between the mother’s breasts to provide uninterrupted adult body heat by means of skin-to-skin contact. Several studies have shown this method to be safe and effective for maintaining body temperature (Bergman and Jurisoo, 1994; Ludington-Hoe et al., 1999; Alisjahbana et al., 1998; Bosque et al., 1995).

Neonatal jaundice/hyperbilirubinemia. In developing countries, neonates with marked jaundice must be promptly referred for treatment to prevent the unconjugated bilirubin from reaching a level that is toxic to the brain. The treatment generally involves phototherapy but may involve exchange transfusion (Joseph and Kramer, 1998).

Corticosteroids have been found to reduce respiratory distress syndrome, reduce intraventricular hemorrhage, and improve the survival of preterm infants when administered to women in preterm labor in random-

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
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ized, controlled trials and case-controlled studies (National Institutes of Health, 1994; Crowley, 1995). The benefits extend across a wide range of gestational ages (24–34 weeks) and are not affected by race or sex. In some developing countries, administration of corticosteroids to women in preterm labor has been recommended as a low-cost, low-technology intervention likely to reduce neonatal morbidity and mortality (Bhutta et al., 1999), especially among larger, more mature preterm infants, who are likely to survive if they do not develop respiratory distress syndrome.

Breastfeeding. Evidence indicates that frequent breastfeeding during the first hours of life can prevent hypoglycemia (Biancuzzo, 1999;Yamauchi and Yamanouchi, 1990). WHO recommends that infants be put to breast within an hour of birth (World Health Organization, 1994). Closeness between mother and infant during breastfeeding may also reduce the risk of hypothermia (Bosque et al., 1995).

Breastfeeding is particularly important where safe, affordable alternatives to breast milk are not available, hygiene is poor, and water is unsafe (Horton et al., 1996; Gupta and Khanna, 1999). The risk of transmitting HIV through breastfeeding is discussed in Chapter 8. Breast milk contains many anti-infective factors, including secretory immunoglobulin A antibodies, lysozyme, lactoferrin, zinc, and receptor analogs for certain epithelial structures that microorganisms need for attachment to host tissue and subsequent infection (Hanson et al., 1994, Hanson et al., 1982). The early initiation of breastfeeding is important because colostrum has higher levels of many anti-infective factors compared with mature milk, and because early feeding helps establish an adequate milk supply. Many studies have documented a reduction in infectious diseases, including sepsis, diarrhea, and pneumonia (Narayanan et al., 1984; Ashraf et al., 1991; Brown et al., 1989; Glezen, 1991), and in infection-related mortality (Betrán et al., 2001; Habicht et al., 1986; Srivastava et al., 1994; Victora et al., 1989, 1987; Daga and Daga, 1989; Sachdev et al., 1991) among infants who are breastfed.

WHO recommends that infants be breastfed exclusively for 6 months (Haider et al., 2000; World Health Organization, 1995). There appears to be no advantage to introducing complementary foods to infants before 4 months of age, and in many places, doing so introduces substantial risk that the infant will develop diarrhea (Cohen et al., 1994). While most women in developing countries breastfeed, many do not do so exclusively throughout this period (Betrán et al., 2001; World Health Organization Collaborative Study Team, 2000). Peer counseling of breastfeeding mothers has been found effective in encouraging exclusive and extended breastfeeding (Haider et al., 2000; Leite et al., 1998; Morrow et al., 1999; Sikorski and Renfrew, 2001). Breastfeeding (defined as exclusive breastfeeding in babies up to 4 months of age) has increased in 21 developing countries, aided by campaigns to publicize the benefits of the practice, prohibition of advertising

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
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and/or distribution of breast milk substitutes, and hospital-based breastfeeding assistance programs (United Nations Children’s Fund, 1999).

Vitamin A supplementation. Providing supplemental vitamin A to very young infants or vitamin A supplements to women during pregnancy has been associated with reductions in postneonatal morbidity and mortality is developed countries (Humphrey et al., 1996; Christian et al., 2001), but not fetal or early neonatal mortality (Katz et al., 2000). Infants are born with very limited stores of vitamin A (less than a 2-week supply) and breastfed infants of well-nourished mothers typically increase their vitamin A stores more than tenfold by their sixth month. However, concentrations of vitamin A in the breast milk of women in developing countries are about half those of well-nourished mothers (Humphrey and Rice, 2000). Studies demonstrate that vitamin A supplements to lactating mothers are efficacious in improving the vitamin A status of their infants (Rice et al., 1999; Stoltzfus et al., 1993), but studies have not evaluated the impact of this intervention on infant mortality.

Neonatal Care
Recognition and treatment of disease

Because untreated illness—especially infection—in newborns can rapidly become life threatening, early identification and treatment of the sick newborn is essential. Efforts are needed to raise family and community awareness regarding danger signs in the neonate and the importance of obtaining care from trained personnel, the availability of services, and the potential impact of medical assistance on neonatal mortality (Ahmed et al., 2001).

An integrated approach to the management of the sick child (IMCI), including young infants, has been developed by WHO and UNICEF (World Health Organization, 1999b; Tulloch, 1999). This approach involves prompt recognition of disease, appropriate therapy using standardized case management, referral of serious cases to health care facilities, and prevention through improved nutrition (including breastfeeding of the neonate) and immunization. Because signs of serious bacterial infection in the newborn are not easily distinguished, newborns with suspected severe infections should be treated. Field studies of IMCI guidelines for neonates have found them to have good sensitivity and moderate specificity. The latter results in overreferral of patients for hospitalization. Continuing development of the guidelines will need to balance the health outcomes for neonates and the ability to handle the additional referrals (Kalter et al., 1997; Gove et al., 1999).

Effective prevention and treatment of neonatal infections requires

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
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knowledge of infectious agents in a community and of their antimicrobial susceptibility. Hospital data, while more commonly available, may not represent the infectious disease burden in the community (Darmstadt et al., 2000). Treatment decisions are based largely on patient history and clinical examination; more accurate prediction of serious infections is needed (WHO Young Infants Study Group, 1999b; Sehgal et al., 1997).

Home-based neonatal care

Studies have evaluated the ability of trained village health workers to identify sick newborns in their homes and to treat them appropriately and in a timely manner. Referral to a hospital is recommended for neonates who are seriously ill; however, initiating antibiotic treatment before the transfer can be lifesaving. Moreover, there will be situations in which referral to a hospital is impossible or unacceptable to the family.

A recent field trial, described in Box 3-1, implemented a program of comprehensive home-based neonatal care in a remote area of rural India (Bang el al., 1999). Care was provided by village health workers with 5 to 10 years of education and overseen by physicians. The success of this intervention in reducing fetal and neonatal mortality rates in a community with limited resources is promising for other low resource settings. Before home-based care is recommended for broad scale implementation, scientifically rigorous trials should test its effectiveness in other settings, along with the cost of initiating and overseeing these programs.

In studies by Bang et al. (1993) and by Datta et al. (1987), caregivers (traditional birth attendants, paramedics, and village health workers) were trained to diagnose neonatal pneumonia using simple clinical signs and symptoms. The caregivers in these studies used a specific case management strategy to manage neonatal pneumonia through the use of antibiotics and continued breastfeeding. Both studies demonstrated a reduction in pneumonia-associated mortality in the community intervention groups.

Neonatal immunization

Maternal and neonatal immunization is an increasingly promising strategy given the threat of antibiotic resistance. In developing countries, however, issues of vaccine cost, availability, delivery, and efficacy in the field are major barriers to the use of vaccines established as safe and effective.

A variety of neonatal immunization strategies have already proven successful. For example, the bacillus Calmette-Guérin (BCG) vaccine—a live attenuated strain of Mycobacterium bovis—is widely used in developing countries where TB is a common and potentially lethal disease. A meta-analysis of BCG studies involving newborns and infants concluded that the

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
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BOX 3-1
Home-Based Neonatal Care in Rural India

High neonatal mortality results from prematurity, birth asphyxia or injury, and infections. Many such deaths could be avoided if neonatal care were available in poor rural communities. A package of comprehensive, home-based neonatal care, including management of sepsis (septicemia, meningitis, and pneumonia), was field-tested in an underdeveloped district of rural India (the Gadchiroli district of Maharashtra State). This intervention reduced perinatal and infant mortality (about 80 per 1000 births in 1994) by nearly 50 percent, at a fraction of the cost of neonatal care in urban areas of India.

Local government health services in the Gadchiroli district provide a male and a female paramedic worker for every 3000 people and a primary care center with two medical doctors for every 20,000 people. Secondary hospitals are located within 30 km of the most remote villages, but do not provide specialized neonatal care. Reproductive health care is sought from private medical practitioners, herbalists, and magic healers.

For this demonstration project, the 39 intervention villages (selected where there were women with 5 to 10 years of education who could be trained to be village health workers) and 47 control villages had similar sociodemographic constitutions and baseline neonatal mortality rates. Resident women in the intervention villages were trained as village health workers.. Each year their training addressed the capabilities needed for interventions to be introduced in the following year. A physician visited each village to verify recorded data and provide supplemental instruction for the health workers, but did not provide care other than referral to the government hospitals available to all patients.

The study involved a baseline phase (April 1993 to March 1995) and an intervention phase (April 1995 to March 1998). In the first intervention year, the village health workers collected data, observed labor and neonates at birth, made regular home visits during the month after birth, weighed the child, and managed minor

vaccine was effective for up to 10 years after infant vaccination, and that it reduced the risk of infection, on average, by more than 50 percent (Colditz et al., 1995). Likewise, hepatitis B vaccination of newborns has been shown to be effective in preventing neonatal infections and their sequelae (Delage et al., 1993). Studies from both industrialized and developing countries have shown that hepatitis B vaccine administered in the immediate newborn period can significantly reduce the rate of neonatal infection and the development of a chronic hepatitis B surface antigen (HBsAg) carrier state (Andre and Zuckerman, 1994). In 1992, WHO recommended that all countries add hepatitis B vaccine to their routine childhood immunization programs (World Health Organization, 2002).

Other promising vaccines require additional research. After successful vaccination of young children against Streptococcus pneumoniae (Obaro et

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
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illnesses and pneumonia. A survey conducted after the first year of this program found that more than 97 percent of parents reported they would seek care from trained female village health workers in the future if their neonate was sick. Given this response, the health workers began the project’s second year by providing home-based management of neonatal illnesses, and, in the following months, neonatal sepsis. In the third year, mothers and grandmothers were educated about the care of pregnant women and their neonates. The complete package was fully functional in the third year of the intervention.

With the neonatal care package entirely in place, neonatal, infant, and perinatal mortality rates dropped by half or more. During the third year of the intervention, an estimated 51 deaths (32 neonatal and 19 fetal) were averted in the villages that received the intervention, based on comparisons with mortality rates in control villages. As 913 neonates received care that year, one death was averted for every 18 neonates who received care. This was accomplished at a cost of US$5.3 per neonate receiving care, a fraction of the cost of neonatal care available in urban Indian hospitals.

The high acceptance of home-based neonatal care in Gadchiroli district was attributed to several factors: the large unmet need for neonatal care; the close involvement of traditional birth attendants; the provision of home care; the successful management of neonatal illness, particularly sepsis; the confidence of parents in the care provided; the emphasis on health education for mothers; the motivated, well-trained, and well-supervised village workers; and the provision of care free of charge. The trained, literate, female village health workers were key to the project’s success. Because they lived in the community, they were not only available and willing to make home visits during labor, delivery, and in the first month postpartum, but were widely accepted in this role.

SOURCE: Bang et al., 1999.

al., 1997; Shinefield et al., 2002), studies in South Africa will evaluate the safety and immunogenicity of protein conjugate pneumococcal vaccines for neonates (Obaro, 2000; Klugman, 2001).

Rotavirus vaccines are being developed to prevent severe diarrheal disease, an important cause of infant and child mortality in developing countries (Glass et al., 1997; Jacobson, 1999; Parashar et al., 1998b). Since children in developing countries experience most severe episodes of rotavirus diarrhea in the first year of life (Cicirello et al., 1994; Kilgore et al., 1996), rotavirus vaccination should be delivered early, possibly at birth (Espinoza et al., 1997; Jacobson, 1999; Cicirello et al., 1994). Further studies are needed on the efficacy and safety of rotavirus vaccines for neonates in developing countries (Cicirello, 1994; Glass et al., 1997; Parashar et al., 1998b).

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
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Care of low-birth-weight infants

One in five infants born in developing countries weighs less than 2,500 grams—the standard for low birth weight (United Nations Children’s Fund, 1999). While survival of the very low-birth-weight infant (< 1,500 grams) is generally tied to intensive-care technology, there are affordable opportunities to improve the management of infants with birth weights between 1,500 and 2,500 grams (see also Chapter 6). The appropriate interventions are similar to those for neonates of normal weight. They include skilled care at delivery and immediate evaluation of the infant at birth; basic neonatal resuscitation when needed; attention to thermal control (drying the infant at birth, Kangaroo care); prevention of hypoglycemia through early breastfeeding; prevention of infection through good domestic hygiene including hand washing; exclusive feeding of breast milk1 (with a cup and spoon if needed); supplementation with vitamins and minerals; growth monitoring; early detection and treatment of illness, particularly presumed bacterial sepsis, pneumonia, or meningitis; frequent home visits by trained health workers to identify signs and symptoms of illness and initiate care or refer to a hospital as needed; and monitoring of breastfeeding, neonatal growth, and overall well-being (Stoll and Measham, 2001). Home-based neonatal care described in Box 3-1 produced a 64 percent reduction in case fatality for low birth weight among neonates in rural India (Bang et al., 1999).

RECOMMENDATIONS

Good quality care for the neonate is critical to reducing infant mortality in developing countries, two-thirds of which occurs during the first 28 days of life. The priorities for reducing neonatal mortality and morbidity parallel those given in Chapter 2 for reducing maternal mortality and morbidity:

  • Lifesaving services for labor and delivery

    • skilled attendant for every birth

    • referral to a health facility with basic or comprehensive essential care as needed for deliveries with complications

  • Key postpartum service

  • Key antenatal services

Recommendation 1. Every delivery, including those that take place in the home, should be assisted by a skilled birth attendant (a midwife, physician, or nurse) who has been trained to proficiency in basic tech-

1  

Perinatal transmission of HIV/AIDS is discussed in Chapter 8.

 

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
×

niques for a clean and safe delivery, recognition and management of prolonged labor and infection; and recognition and resuscitation of neonates who fail to initiate respiration at birth. Where necessary, the birth attendant should also be prepared to stabilize and swiftly refer the neonate to a facility providing essential obstetric and neonatal care.2 (See Chapter 2 for the maternal component of this recommendation.)

Recommendation 2. Essential neonatal care should be accessible to address all complications of childbirth that cannot be managed by a skilled birth attendant. This requires a network of good quality essential care facilities. Services for essential neonatal care should emphasize the diagnosis and treatment of infection. Access for the majority of a population to the appropriate level of care also requires strong referral systems that include communication with, and transportation to, referral facilities. (See Chapters 2 and 5 for other components of this recommendation.)

Recommendation 3. Postpartum care is critical during the first hours after birth and important throughout the first month. For the neonate, such care should emphasize: the prevention, timely recognition, and treatment of infection, thermal control, and promotion and support of early and exclusive breastfeeding. (See Chapter 2 for the maternal component of this recommendation and Chapter 8 for discussion of breastfeeding in populations with a high prevalence of HIV.)

The following antenatal interventions target the major causes of neonatal mortality and morbidity that are covered in this chapter.

Recommendation 4. The following strategies are recommended for incorporation into preconceptional and antenatal care:

  • Immunization against tetanus for all women of reproductive age.

  • Early detection and timely treatment of syphilis and other STDs, asymptomatic bacteriuria/urinary tract infection, and tuberculosis.

(See Chapters 2, 6, 7, and 8 for other components of this recommendation.)

RESEARCH NEEDS

In addition to research priorities identified in Chapter 2 as important to improving all birth outcomes, the committee identified the following topics as priorities for reducing neonatal mortality and morbidity:

2  

This issue is also discussed in Appendix E, Dissenting Note by Dr. Abhay Bang.

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
×
  • Several vaccines are being developed or are under evaluation for prevention of mother-to-child transmission of infection (e.g., group B streptococcus, cytomegalovirus, Haemophilus influenzae, Streptococcus pneumoniae). Further studies are warranted; such studies must first address safety of the mother, fetus, and young infant, and evaluate protection against the target disease, as well as other causes of mortality. The subsequent response of the infant to active immunization with routine childhood vaccines must also be monitored to ensure that maternal immunization does not hamper the infant’s ability to respond to vaccines.

  • Studies are needed to determine the optimal strategy to reduce the neonatal impact of STDs in pregnancy in developing countries. This might involve presumptive therapy for all pregnant women or the development of cost-effective diagnostic tests that can be used in field settings to facilitate prompt maternal therapy.

  • With the exception of HIV, there is a paucity of data from developing countries on the burden of intrauterine, intrapartum, and/or postnatal infections of importance to newborns. These infections include tuberculosis, syphilis, cytomegalovirus, herpes virus, toxoplasmosis, hepatitis C, and malaria. Targeted studies of newborns are warranted in selected areas with known high rates of infection among adults.

  • Hospital-based surveillance systems are needed to determine the rates of hospital-acquired infections for infants born in hospital, as well as for those born at home and referred to hospital for care. In addition to birth-weight-specific rates of infection, surveillance should include the spectrum of pathogens isolated, antibiotic treatment, antibiotic susceptibility, and case fatality rates. This is particularly relevant in an era when the promotion of institutional births to reduce maternal mortality may result in more newborns in hospital.

  • A simple package of measures to control neonatal infection should be evaluated in low-income hospital settings. The package would include hand washing (available soap, water, and clean disposable towel vs. an agent such as chlorhexidene vs. quick-drying spirit to clean hands without the need for soap, water, or towel); neonatal skin care, including umbilical cord care; clean bassinets or isolettes, and clean clothes and blankets; reduction in nursery crowding; strict guidelines for the use of intravenous fluids and intravenous antibiotics (since reducing the number of infants who require intravenous lines would reduce the rates of bloodstream infection); and exclusive breastfeeding (either directly from the breast or with a clean cup and spoon when an infant cannot suck). See also Chapter 8 re women infected with HIV.

  • Research should be conducted to determine the incidence and prevalence of neonatal asphyxia in different geographic regions and settings; whether basic neonatal resuscitation can be implemented safely at the vil-

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
×

lage/home level and if so, how to monitor its effectiveness; and what short-and long-term impacts training of health workers in basic neonatal resuscitation would have on birth outcomes.

  • A management package for home-based neonatal and postpartum maternal care should be evaluated in several geographic areas in both rural and urban settings. Research should address issues such as beliefs and practices regarding labor, childbirth, and care of the neonate; selection, training, supervision, and evaluation of health workers to provide home-based care; impact of home care on neonatal and maternal mortality; and cost-benefit analyses.

  • Studies are needed to evaluate the efficacy of simple, inexpensive, culturally acceptable regimens for care of the umbilical cord immediately following delivery and in the days until the cord separates. Potential interventions include topical antibiotic versus antiseptic agents, and cord ties versus plastic clamps. Evaluations should include rates of omphalitis, neonatal sepsis, neonatal tetanus, and death. Researchers should also examine whether topical antibiotic treatment of the umbilical cord complements maternal tetanus toxoid immunization and further reduces the risk of neonatal tetanus in countries where that disease is prevalent.

  • Hospital-based and community studies with accurate laboratory evaluations are needed to determine the etiologic agents responsible for serious infections in neonates (i.e., both early-onset and late-onset sepsis and meningitis). Surveillance of antibiotic use patterns in different settings (urban vs. rural; community health centers vs. hospitals) is needed to ensure appropriate use of those drugs.

  • Research should be encouraged to develop cost-effective health care technology for neonates in low-resource settings that is inexpensive; easy to use; and, if possible, manufactured locally. Existing examples of such tools include mask-and-tube devices for neonatal resuscitation and Kangaroo care to prevent hypothermia.

CONCLUSION

Growing recognition of the magnitude of neonatal mortality and morbidity in developing countries highlights the need for health care interventions that specifically target the newborn. The basic improvements in care that could significantly improve neonatal survival include:

  • Antenatal care that includes immunization against tetanus, intermittent preventive treatment of malaria, and early detection and timely treatment of malaria, tuberculosis, syphilis, and asymptomatic bacteriuria or urinary tract infection.

  • Clean and safe delivery by a skilled attendant who can perform basic

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
×

resuscitation, prevent hypothermia, support early and frequent breastfeeding, recognize serious complications, and provide prompt effective referral to a facility providing essential obstetric and neonatal care.

  • Routine neonatal care at home by the mother and family members who have received instruction in clean and safe neonatal care practices. In the event of serious illness, especially systemic infection, prompt evaluation and therapy can save lives. If referral is not possible or acceptable, home-based management of the condition becomes important.

While the interventions recommended in this chapter target the neonate, most either complement or build upon previous recommendations to improve maternal outcomes. Together these services provide the foundation for a comprehensive program of care that can significantly improve maternal and neonatal health and also fetal survival.

REFERENCES

Adhikari M, Pillay T, Pillay DG. 1997. Tuberculosis in the newborn: an emerging disease. Pediatric Infectious Disease Journal 16(12):1108–1112.

Ahmed S, Sobhan F, Islam A, Barkat-e-Khuda. 2001. Neonatal morbidity and care-seeking behavior in rural Bangladesh. Journal of Tropical Pediatrics 47(2):98–105.

Ahmed Y, Mwaba P, Chintu C, Grange GM, Ustianowski A, Zumia A.1999. A study of maternal mortality at the University Teaching Hospital, Lusaka, Zambia: the emergence of tuberculosis as a major non-obstetric cause of maternal death. International Journal of Tuberculosis and Lung Disease 8:675–680.

Akaba K, Kimura T, Sasaki A, Tanabe S, Ikegami T, Hashimoto M, Umeda H, Yoshida H, Umetsu K, Chiba H, Yuasa I, Hayasaka K. 1998. Neonatal hyperbilirubinemia and mutation of the bilirubin uridine diphosphate-glucuronosyltransferase gene: a common missense mutation among Japanese, Koreans and Chinese. Biochemistry and Molecular Biology International 46(1):21–26.

Ako-Nai AK, Adejuyigbe EA, Ajayi FM, Onipede AO. 1999. The bacteriology of neonatal septicaemia in Ile-Ife, Nigeria. Journal of Tropical Pediatrics 45(3):146–151.

Alisjahbana A, Usman A, Irawaty S, Triyati A. 1998. Prevention of hypothermia of low birth weight infants using the kangaroo method. Paediatrica Indonesiana 38:205–215.

Alisjahbana A, Hidayat S, Mintardaningsih, Primadi A, Harliany E, Sofiatin Y, Triyanti A. 1999. Management of birth-asphyxia at home and health center. Pediatric Indonesiana 39:88–91.

Alpay F, Sarici SU, Tosuncuk HD, Serdar MA, Inanc N, Gokcay E. 2000. The value of first-day bilirubin measurement in predicting the development of significant hyperbilirubinemia in healthy term newborns. Pediatrics 106(2):E16.

Andre FE, Zuckerman AJ. 1994. Review: protective efficacy of hepatitis B vaccines in neonates. Journal of Medical Virology 44(2):144–151.

Anonymous. 2000. ACOG practice bulletin: management of herpes in pregnancy. International Journal of Gynaecology and Obstetrics 68(2):165–173.

Ashraf RN, Jalil F, Zaman S, Karlberg J, Khan SR, Lindblad BS, Hanson LA. 1991. Breast feeding and protection against neonatal sepsis in a high risk population. Archives of Disease in Childhood. Fetal and Neonatal Edition 66(4):488–490.

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
×

Asindi AA, Bilal NE, Fatinni YA. 1999. Neonatal septicemia. Saudi Medical Journal 20:942–946 .

Aye DT, Bact D, Sack DA, Wachsmuth IK, Kyi DT, Thwe SM. 1991. Neonatal diarrhea at a maternity hospital in Rangoon. American Journal of Public Health 81(4):480–481.


Banerjee M, Sahu K, Bhattacharya S, Adhya S, Bhowmick P, Chakraborty P. 1993. Outbreak of neonatal septicemia with multidrug resistant Klebsiella pneumoniae. Indian Journal of Pediatrics 60(1):25–27.

Bang AT, Bang RA, Morankar VP, Sontakke PG, Solanki JM. 1993. Pneumonia in neonates: can it be managed in the community? Archives of Disease in Childhood. Fetal and Neonatal Edition 68(5 Spec No):550–556.

Bang AT, Bang RA, Baitule SB, Reddy MH, Deshmukh MD. 1999. Effect of home-based neonatal care and management of sepsis on neonatal mortality: field trial in rural India. Lancet 354(9194):1955–1961.

Bang AT, Bang RA, Baitule S, Deshmukh M, Reddy MH. 2001. Burden of morbidities and the unmet need for health care in rural neonates: a prospective observational study in Gadchiroli, India. Indian Pediatrics 38:952–967.

Bell DM. 2001. Promoting appropriate antimicrobial drug use: perspective from the Centers from Disease Control and Prevention. Clinical Infectious Diseases 33(suppl 3):S245– S250.

Benitz WE, Gould JB, Druzin ML. 1999. Antimicrobial prevention of early-onset group B streptococcal sepsis: estimates of risk reduction based on a critical literature review. Pediatrics 103(6):E78.

Bennett J, Macia J, Traverso H, Banoagha S, Malooly C, Boring J. 1997. Protective effects of topical antimicrobials against neonatal tetanus. International Journal of Epidemiology 26(4):897–903.

Bergman NJ, Jurisoo LA. 1994. The “kangaroo-method” for treating low birth weight babies in a developing country. Tropical Doctor 24(2):57–60.

Bergsjo P, Villar J. 1997. Scientific basis for the content of routine antenatal care. II. Power to eliminate or alleviate adverse newborn outcomes: some special conditions and examinations. Acta Obstetricia et Gynecologica Scandinavica 76(1):15–25.

Bern C, Martines J, de Zoysa I, Glass RI. 1992. The magnitude of the global problem of diarrhoeal disease: a ten-year update. Bulletin of the World Health Organization 70(6):705–714.

Betrán AP, de Onis M, Lauer J, Villar J. 2001. Ecological study of effect of breastfeeding on infant mortality in Latin America. British Medical Journal 323(7308):303–306.

Bhutta ZA. 1996. Enterobacter sepsis in the newborn—a growing problem in Karachi. Journal of Hospital Infection 34(3):211–216.

Bhutta ZA, Yusuf K, Khan IA. 1999. Is management of neonatal respiratory distress syndrome feasible in developing countries? Experience from Karachi (Pakistan). Pediatric Pulmonology 27(5):305–311.

Biancuzzo M. 1999. Breastfeeding the Newborn Clinical Strategies for Nurses. St. Louis, MO: Mosby.

Bicego GT, Boerma JT. 1993. Maternal education and child survival: a comparative study of survey data from 17 countries. Memoires de la Societe des Sciences Medicales de Lille 36(9):1207–1227.

Bisgard KM, Kao A, Leake J, Strebel PM, Perkins BA, Wharton M. 1998. Haemophilus influenzae invasive disease in the United States, 1994-1995: near disappearance of a vaccine-preventable childhood disease. Emerging Infectious Diseases 4(2):229–237.

Bloom SS, Lippeveld T, Wypij D. 1999. Does antenatal care make a difference to safe delivery? A study in urban Uttar Pradesh, India. Journal of the American Medical Association 14(1):38–48.

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
×

Boo NY, Lye MS. 1991. Factors associated with clinically significant perinatal asphyxia in the Malaysian neonates: a case-control study. Journal of Tropical Pediatrics 38(6):284–249.

Bosque EM, Brady JP, Affonso DD, Wahlberg V. 1995. Physiologic measures of kangaroo versus incubator care in a tertiary-level nursery. Journal of Obstetrics and Gynecology Neonatal Nursing 24(3):219–226.

Bosu WK, 1999. Syndromic management of sexually transmitted diseases: is it rational or scientific? Tropical Medicine and International Health 4(2):114–119.

Boyce JM. 2001. Consequences of infection: importance of infection control practices. Clinical Infectious Diseases 33(suppl 3):S133–S137.

Brkic S, Jovanovic J. 1998. Genital herpes with special emphasis on perinatal herpes simplex virus. [in Serbo-Croatian (Roman)]. Medicinski Pregled 51(1–2):45–49.

Brown KH, Black RE, Lopez de Romana G, Creed de Kanashiro H. 1989. Infant-feeding practices and their relationship with diarrheal and other diseases in Huascar (Lima), Peru. Pediatrics 83(1):31–40.

Brown ZA, Vontver LA, Benedetti J, Critchlow CW, Sells CJ, Berry S, Corey L. 1987. Effects on infants of a first episode of genital herpes during pregnancy. New England Journal of Medicine 317(20):1246–1251.

Brown ZA, Benedetti J, Selke S, Ashley R, Watts DH, Corey L. 1996. Asymptomatic maternal shedding of herpes simplex virus at the onset of labor: relationship to preterm labor. Obstetrics and Gynecology 87(4):483–488.


Carroli G, Rooney C, Villar J. 2001a. WHO Programme to map the best reproductive health practices: how effective is antenatal care in preventing maternal mortality and serious morbidity? Paediatric and Perinatal Epidemiology 15(suppl 1):1–42.

Carroli G, Villar J, Piaggio G, Khan-Neelofur D, Gülmezoglu M, Mugford M, Lumbiganon P, Farnot U, Bersgjo P, WHO Antenatal Care Trial Research Group. 2001b. WHO systematic review of randomised controlled trials of routine antenatal care. Lancet 357(9268):1565–1570.

Cashore WJ. 1994. Neonatal hyperbilirubinemia. In: Oski FA, DeAngelis CD, Feigin RD, Warshaw JB (eds). Principles and Practice of Pediatrics, Second Edition. Philadelphia: Lippincott Company. Pp. 446–455.

Chandra S, Ramji S, Thirupuram S. 1997. Perinatal asphyxia: multivariate analysis of risk factors in hospital births. Indian Pediatrics 34(3):206–212.

Chaturvedi P, Shah N. 1991. Fetal co-relates and mode of delivery in asphyxia neonatorum. Indian Journal of Pediatrics 58(1):63–67.

Child Health Research Project Special Report. 1999. Reducing Perinatal and Neonatal Mortality: Report of a Meeting, Baltimore, Maryland, May 10-12 1999. Baltimore, MD: Child Health Research Project.

Choudhary SP, Bajaj RK, Gupta RK. 2000. Knowledge, attitude and practices about neonatal hypothermia among medical and paramedical staff. Indian Journal of Pediatrics 67(7):491–496.

Christian P, West KP, Khatry SK, LeClerq, Kimbrough-Pradhan E, Katz J, Shrestha SR. 2001. Maternal night blindness increases risk of mortality in the first 6 months of life among infants in Nepal. Journal of Nutrition 131(5):1510–1512.

Cicirello HG, Das BK, Gupta A, Bhan MK, Gentsch JR, Kumar R, Glass RI. 1994. High prevalence of rotavirus infection among neonates born at hospitals in Delhi, India: predisposition of newborns for infection with unusual rotavirus. Pediatric Infectious Disease Journal 13(8):720–724.

Cohen RJ, Brown KKH, Canahuati J, Rivera LL, Dewey KG. 1994. Effects of age of introduction of complementary foods on infant breast milk intake, total energy intake, and growth: a randomised intervention study in Honduras. Lancet 344(8932):1205.

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
×

Colditz GA, Berkey CS, Mosteller F, Brewer TF, Wilson ME, Burdick E, Fineberg HV. 1995. The efficacy of bacillus Calmette-Guerin vaccination of newborns and infants in the prevention of tuberculosis: meta-analyses of the published literature. Pediatrics 96(1 Pt 1):29–35.

Connelly Smith K. 2002. Congenital tuberculosis: a rare manifestation of a common infection. Current Opinion in Infectious Diseases 15(3):269–274.

Crowley PA. 1995. Antenatal corticosteroid therapy: a meta-analysis of the randomized trials, 1972 to 1994. American Journal of Obstetrics and Gynecology 173(1):322–335.

Cushing AH. 1985. Omphalitis: a review. Pediatric Infectious Diseases 4(3):282–285.


Daga AS, Daga SR, Patole SK. 1990. Risk assessment in birth asphyxia. Journal of Tropical Pediatrics 36(1):34–39.

Daga SR, Daga AS. 1989. Reduction in neonatal mortality with simple interventions. Journal of Tropical Pediatrics 35(4):191–196.

Dagan R, Gorodischer R. 1984. Infections in hypothermic infants younger than 3 months old. American Journal of Diseases of Children 138(5):483–485.

Darmstadt GL, Black RE, Santosham M. 2000. Research priorities and postpartum care strategies for the prevention and optimal management of neonatal infections in less developed countries. Pediatric Infectious Disease Journal 19(8):739–750.

Datta N, Kumar V, Kumar L, Singhi S. 1987. Application of case management to the control of acute respiratory infections in low-birth-weight infants: a feasibility study. Bulletin of the World Health Organization 65(1):77–82.

Davidson PT. 1995. Managing tuberculosis during pregnancy. Lancet 346(8969):199–200.

Davies-Adetugbo AA, Torimiro SE, Ako-Nai KA. 1998. Prognostic factors in neonatal tetanus. Tropical Medicine and International Health 3(1):9–13.

de Man P, Verhoeven BA, Verbrugh HA, Vos MC, van den Anker JN. 2000. An antibiotic policy to prevent emergence of resistant bacilli. Lancet 355(9208):973–978.

de Moraes-Pinto MI, Oruamabo RS, Igbagiri FP, Chan MC, Prado SM, Vancetto MD, Johnson PM, Hart CA. 1995. Neonatal tetanus despite immunization and protective antitoxin antibody. Journal of Infectious Diseases 171(4):1076–1077.

Delage G, Remy-Prince S, Montplaisir S. 1993. Combined active-passive immunization against the hepatitis B virus: five-year follow-up of children born to hepatitis B surface antigen-positive mothers. Pediatric Infectious Disease Journal 12(2):126–130.

Dempsey C, Harrison RFF, Moloney A, Darling M, Walshe J. 1992. Characteristics of bacteriuria in a homogeneous maternity hospital population. European Journal of Obstetrics, Gynecology, and Reproductive Biology 44:189–93.

Dennery PA, Seidman DS, Stevenson DK. 2001. Drug therapy: neonatal hyperbilirubinemia. New England Journal of Medicine 344(8):581–590.

Deorari AK, Paul VK, Singh M, Vidyasagar D. 2000. The National Movement of Neonatal Resuscitation in India. Journal of Tropical Pediatrics 46(5):315–317.

Desenclos JC, Garrity D, Scaggs M, Wroten JE. 1992. Gonococcal infection of the newborn in Florida, 1984-1989. Sexually Transmitted Diseases 19(2):105–110.

Dorfman DH, Glaser JH. 1990. Congenital syphilis presenting in infants after the newborn period. New England Journal of Medicine 323(19):1299–1302.

Dragovich D, Tamburlini G, Alisjahbana A, Kambarami R, Karagulova J, Lincetto O, Malla DS, Mello MJ, Vani NS. 1997. Thermal control of the newborn: knowledge and practice of health professional in seven countries. Acta Paediatrica 86(6):645–650.


Egri-Okwaji MT, Iroha EO, Kesah CN, Odugbemi TO. 1998. Bacteria causing septicaemia in neonates with tetanus. West African Journal of Medicine 17(3):136–139.

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
×

Ellis M, Manandhar N, Shakya U, Manandhar DS, Fawdry A, Costello AM. 1996. Postnatal hypothermia and cold stress among newborn infants in Nepal monitored by continuous ambulatory recording. Archives of Disease in Childhood. Fetal and Neonatal Edition. 75(1):F42–F45.

Ellis M, Manandhar N, Shrestha PS, Shrestha L, Manandhar DS, Costello AM. 1999. Outcome at 1 year of neonatal encephalopathy in Kathmandu, Nepal. Developmental Medicine and Child Neurology 41(10):689–695.

Ellis M, Manandhar DS, Manandhar N, Wyatt J, Bolam AJ, Costello AM. 2000. Stillbirths and neonatal encephalopathy in Kathmandu, Nepal: an estimate of the contribution of birth asphyxia to perinatal mortality in a low-income urban population. Paediatric Perinatal Epidemiology 14(1):39–52.

Espinoza F, Paniagua M, Hallander H, Svensson L, Strannegard O. 1997. Rotavirus infections in young Nicaraguan children. Pediatric Infectious Disease Journal 16(6):564–571.


Faridi MM, Rattan A, Ahmad SH. 1993. Omphalitis neonatorum. Journal of the Indian Medical Association 91(11):283–285.

Fleming DT, Wasserheit JN. 1999. From epidemiological synergy to public health policy and practice: the contribution of other sexually transmitted diseases to sexual transmission of HIV infection. Sexually Transmitted Infections 75(1):3–17.

Frank D, Duke T. 2000. Congenital syphilis at Goroka Base Hospital: incidence, clinical features and risk factors for mortality. Papua New Guinea Medical Journal 43(1–2):121–126.


Galazka A, Stroh G. 1986. Neonatal Tetanus Guidelines on the Community-Based Survey on Neonatal Tetanus Mortality. Geneva: WHO.

Garenne M, Ronsmans C, Campbell H. 1992. The magnitude of mortality from acute respiratory infections in children under 5 years in developing countries. World Health Statistics Quarterly 45(2–3):180–191.

Garner P, Lai D, Baea M, Edwards K, Heywood P. 1994. Avoiding neonatal death: an intervention study of umbilical cord care. Journal of Tropical Pediatrics 40(1):24–28.

Gasse F. 1995. Neonatal tetanus: review of progress. International Journal of Gynecology and Obstetrics 50(suppl 2):S67–S72.

Gerbase AC, Rowley JT, Heymann DH, Berkley SF, Piot P. 1998. Global prevalence and incidence estimates of selected curable STDs. Sexually Transmitted Infections 74(suppl 1):S12–S16.

Gibbs RS, Dinsmoor MJ, Newton ER, Ramamurthy RS. 1988. A randomized trial of intrapartum versus immediate postpartum treatment of women with intra-amniotic infection. Obstetrics and Gynecology 72(6):823–828.

Gilson L, Mkanje R, Grosskurth H, Mosha F, Picard J, Gavyole A, Todd J, Mayaud P, Swai R, Fransen L, Mabey D, Mills A, Hayes R. 1997. Cost-effectiveness of improved treatment services for sexually transmitted diseases in preventing HIV-1 infection in Mwanza Region, Tanzania. Lancet 350:1805–1809.

Glass RI, Bresee JS, Parashar U, Miller M, Gentsch JR. 1997. Rotavirus vaccines at the threshold. Nature Medicine 3(12):1324–1335.

Glezen WP. 1991. Epidemiological perspective of breastfeeding and acute respiratory illnesses in infants. Advances in Experimental Medicine and Biology 310:235–240.

Glezen WP, Alpers M. 1999. Maternal immunization. Clinical Infectious Diseases 28(2):219–224.

Gloyd S, Chai S, Mercer MA. 2001. Antenatal syphilis in sub-Saharan Africa: missed opportunities for mortality reduction. Health Policy and Planning 16(1):29–34.

Gomwalk NE, Gosham LT, Umoh UJ. 1990. Rotavirus gastroenteritis in pediatric diarrhoea in Jos, Nigeria. Journal of Tropical Pediatrics 36(2):52–55.

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
×

Gourley GR. 1997. Bilirubin metabolism and kernicterus. Advances in Pediatrics 44:173–229.

Gove S, Tamburlini G, Molyneux E, Whitesell P, Campbell H. 1999. Development and technical basis of simplified guidelines for emergency triage assessment and treatment in developing countries. WHO Integrated Management of Childhood Illness (IMCI) Referral Care Project. Archives of Disease in Childhood 81(6):473–477.

Gray RH, Wabwire-Mangen F, Kigozi G, Sewankambo NK, Serwadda D, Moulton LH, Quinn TC, O’Brien KL, Meehan M, Abramowsky C, Robb M, Wawer MJ. 2001. Randomized trial of presumptive sexually transmitted disease therapy during pregnancy in Rakai, Uganda. American Journal of Obstetrics and Gynecology 185(5):1209–1217.

Grosskurth H, Mosha F, Todd J, Mwijarubi E, Klokke A, Senkoro K, Mayaud P, Changalucha J, Nicoll A, ka-Gina G, et al. 1995. Impact of improved treatment of sexually transmitted diseases on HIV infection in rural Tanzania: randomised controlled trial. Lancet 346(9094):530–536.

Gupta A, Khanna K. 1999. Economic value of breastfeeding in India. National Medical Journal of India 12(3):123–127.

Gupta SD, Keyl PM. 1998. Effectiveness of prenatal tetanus toxoid immunization against neonatal tetanus in a rural area in India. Pediatric Infectious Disease Journal 17(4):316–321.

Gurkan F, Bosnak M, Dikici B, Bosnak V, Tas MA, Haspolat K, Kara IH, Ozkan I. 1999. Neonatal tetanus: a continuing challenge in the southeast of Turkey: risk factors, clinical features and prognostic factors. European Journal of Epidemiology 15(2):171–174.


Habicht JP, DaVanzo J, Butz WP. 1986. Does breastfeeding really save lives, or are apparent benefits due to biases? American Journal of Epidemiology 123(2):279–290.

Haddad Q, Sobayo EI, Basit OB, Rotimi VO. 1993. Outbreak of methicillin-resistant Staphylococcus aureus in a neonatal intensive care unit. Journal of Hospital Infection 23(3):211–222.

Haffejee IE. 1995. The epidemiology of rotavirus infections: a global perspective. Journal of Pediatric Gastroenterology and Nutrition 20(3):275–286.

Haider R, Ashworth A, Kabir I, Huttly SR. 2000. Effect of community-based peer counsellors on exclusive breastfeeding practices in Dhaka, Bangladesh: a randomised controlled trial. Lancet 356(9242):1643–1647.

Hansen TW, Bratlid D. 1986. Bilirubin and brain toxicity. Acta Paediatrica Scandinavica 75(4):513–522.

Hanson LA, Brinton C, Carlsson B, Dahlgren U, Mellander L, Sutton A, Soderstrom T. 1982. The mucosal immune response in the neonate. Acta Paediatrica Scandinavia 296(suppl):53–55.

Hanson LA, Ashraf R, Zaman S, Karlberg J, Lindblad BS, Jalil F. 1994. Breast feeding is a natural contraceptive and prevents disease and death in infants, linking infant mortality and birth rates. Acta Paediatrica Scandinavia 83(1):3–6.

Hira SK, Bhat GJ, Chikamata DM, Nkowane B, Tembo G, Perine PL. 1990. Syphilis intervention in pregnancy: Zambian demonstration project. Genitourinary Medicine 66:159–164.

Hlady WG, Bennett JV, Samadi AR, Begum J, Hafez A, Tarafdar AI, Boring JR. 1992. Neonatal tetanus in rural Bangladesh: risk factors and toxoid efficacy. American Journal of Public Health 82(10):1365–1369.

Horton S, Sanghvi T, Phillips M, Fiedler J, Perez-Escamilla R, Lutter C, Rivera A, Segall-Correa AM. 1996. Breastfeeding promotion and priority setting in health. Health Policy and Planning 11(2):156–168.

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
×

Humphrey JH, Agoestina T, Wu L, Usman A, Nurachim M, Subardja D, Hidayat S, Tielsch J, West KP, Sommer A. 1996. Impact of neonatal vitamin A supplementation on infant morbidity and mortality. Journal of Pediatrics 128(4):489–496.

Humphrey JH, Rice AL. 2000. Vitamin A supplementation of young infants. Lancet 356(9227):422–424.


Jacobs RF. 1998. Neonatal herpes simplex virus infections. Seminars in Perinatology 22(1):64–71.

Jacobson RM. 1999. The current status of the rotavirus vaccine. Vaccine 17(13-14):1690–1699.

Jamil K, Bhuiya A, Streatfield K, Chakrabarty N. 1999. The immunization programme in Bangladesh: impressive gains in coverage, but gaps remain. Health Policy and Planning 14(1):49–58.

Jana N, Vasishta K, Jindal SK, Khunnu B, Ghosh K. 1994. Perinatal outcome in pregnancies complicated by pulmonary tuberculosis. International Journal of Gynaecology and Obstetrics 44(2):119–124.

Jeena PM, Coovadia HM, Gouws E. 1997. Risk factors for neonatal tetanus in KwaZulu-Natal. South African Medical Journal 87(1):46–48.

Joseph KS, Kramer MS. 1998. The decline in Rh hemolytic disease: should Rh prophylaxis get all the credit? American Journal of Public Health 88:209–215.


Kalter HD, Schillinger JA, Hossain M, Burnham G, Saha S, de Wit V, Khan NZ, Schwarts B, Black RE. 1997. Identifying sick children requiring referral to hospital in Bangladesh. Bulletin of the World Health Organization 75(suppl 1):65–75.

Katz J, West KP Jr, Khatry SK, Pradhan EK, LeClerq SC, Christian P, Wu LS, Adhikari RK, Shrestha SR, Sommer A. 2000. Maternal low-dose vitamin A or β-carotene supplementation has no effect on fetal loss and early infant mortality: a randomized cluster trial in Nepal. American Society for Clinical Nutrition 71(16):1570–1576.

Kilgore PE, Unicomb LE, Gentsch JR, Albert MJ, McElroy CA, Glass RI. 1996. Neonatal rotavirus infection in Bangladesh: strain characterization and risk factors for nosocomial infection. Pediatric Infectious Disease Journal 15(8):672–677.

Kinoti SN. 1993. Asphyxia of the newborn in east, central and southern Africa. East African Medical Journal 70(7):422–433.

Klugman KP. 2001. Efficacy of pneumococcal conjugate vaccines and their effect on carriage and antimicrobial resistance. Lancet Infectious Diseases 1(2):85–91.

Koenig MA, Roy NC, McElrath T, Shahidullah M, Wojtyniak B. 1998. Duration of protective immunity conferred by maternal tetanus toxoid immunization: further evidence from Matlab, Bangladesh. American Journal of Public Health 88(6):903–907.

Korbage de Araujo MC, Schultz R, do Rosario Dias de Oliveira L, Ramos JL, Vaz FA. 1999. A risk factor for early-onset infection in premature newborns: invasion of chorioamniotic tissues by leukocytes. Early Human Development 56(1):1–15.

Kuruvilla KA, Pillai S, Jesudason M, Jana AK. 1998. Bacterial profile of sepsis in a neonatal unit in south India. Indian Pediatrics 35(9):851–858.


Laga M, Plummer FA, Piot P, Datta P, Namaara W, Ndinya-Achola JO, Nzanze H, Maitha G, Ronald AR, Pamba HO. 1988. Prophylaxis of gonococcal and chlamydial ophthalmia neonatorum. A comparison of silver nitrate and tetracycline. New England Journal of Medicine 318(11):653–657.

Lawn J, McCarthy BJ, Ross S. 2001. The Healthy Newborn: A Reference Manual for Program Managers. Atlanta, GA: CDC/CARE.

Lehmann D, Pomat WS, Combs B, Dyke T, Alpers MP. 2002. Maternal immunization with pneumococcal polysaccharide vaccine in the highlands of Papua New Guinea. Vaccine 20(13-14):1837–1845.

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
×

Leite AJM, Puccini R, Atallah A. 1998. Impact on breastfeeding practices promoted by lay counselors: a randomised and controlled trial. Journal of Clinical Epidemiology 51:S10.

Levy SB. 2001. Antibiotic resistance: consequences of inaction. Clinical Infectious Diseases 33(suppl 3):S124–S129.

Ludington-Hoe SM, Anderson GC, Simpson S, Hollingsead A, Argote LA, Rey H. 1999. Birth-related fatigue in 34-36-week preterm neonates: rapid recovery with very early kangaroo (skin-to-skin) care. Journal of Obstetrics and Gynecologic and Neonatal Nursing 28(1):94–103.

Lumbiganon P, Piaggio G, Villar J, Pinol A, Bakketeig L, Bergsjo P, Al-Mazrou Y, Ba’aqeel H, Belizan JM, Farnot U, Carroli G, Berendes H, WHO Antenatal Care Trial Research Group. 2002. The epidemiology of syphilis in pregnancy. International Journal of STD and AIDS 13(7):486–494.

Luther NY. 1998. Mother’s tetanus immunisation is associated not only with lower neonatal mortality but also with lower early-childhood mortality. National Family Health Survey Bulletin (10):1–4.


Manzar S. 1999. Role of hypothermia in asphyxia. Pediatrics 104(5 Pt 1):1169.

Martius JA, Roos T, Gora B, Oehler MK, Schrod L, Papadopoulos T, Gross U. 1999. Risk factors associated with early-onset sepsis in premature infants. European Journal of Obstetrics, Gynecology, and Reproductive Biology 85(2):151–158.

Massawe A, Kilewo C, Irani S, Verma RJ, Chakrapam AB, Ribbe T, Tunell R, Fischler B. 1996. Assessment of mouth-to-mask ventilation in resuscitation of asphyxic newborn babies. A pilot study. Tropical Medicine and International Health 1(6):865–873.

Mayaud P, Grosskurth H, Changalucha J, Todd J, West B, Gabone R, Senkoro K, Rusizoka M, Laga M, Hayes R. 1995. Risk assessment and other screening options for gonorrhoea and chlamydial infections in women attending rural Tanzanian antenatal clinics. Bulletin of the World Health Organization 73(5):621–630.

Mayaud P, Ka-Gina G, Grosskurth H. 1998. Effectiveness, impact and cost of syndromic management of sexually transmitted diseases in Tanzania. International Journal of STD and AIDS 9(suppl 1):11–14.

McCarroll JR, Abrahams I, Skudder PA. 1962. Antibody response to tetanus toxoid 15 years after initial immunization. American Journal of Public Health 52:1669–1675.

Mercer BM, Miodovnik M, Thurnau GR, Goldenberg RL, Das AF, Ramsey RD, Rabello Ya, Meis PJ, Moawad AH, Iams JD, Van Dorsten JP, Paul RH, Bottoms SF, Merenstein G, Thom EA, Roberts HM, Mc Nellis D. 1998. Antibiotic therapy for reduction of infant morbidity after preterm premature rupture of the membranes: a randomized controlled trial. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Journal of the American Medical Association 278(12):989–995.

Milner AD, Upton CJ, Green J, Stokes GM. 1990. A device for domiciliary neonatal resuscitation. Lancet 335(8684):273–275.

Misra S, Bhakoo ON, Ayyagiri A, Katariya S. 1991. Clinical and bacteriological profile of neonatal pneumonia. Indian Journal of Medical Research 93:366–370.

Mlay GS, Manji KP. 2000. Respiratory distress syndrome among neonates admitted at Muhimbili Medical Centre, Dar es Salaam, Tanzania. Journal of Tropical Pediatrics 46(5):303–307.

Monto AS, Lehmann D. 1998. Acute respiratory infections (ARI) in children: prospects for prevention. Vaccine 16(16):1582–1588.

Moodley P, Sturm AW. 2000. Sexually transmitted infections, adverse pregnancy outcome and neonatal infection. Seminars in Neonatology 5(3):255–269.

Moreno MT, Vargas S, Poveda R, Saez-Llorens X. 1994. Neonatal sepsis and meningitis in a developing Latin American country. Pediatric Infectious Disease Journal 13(6):516–520.

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
×

Morrow AL, Guerrero ML, Shults J, Calva JJ, Lutter C, Bravo J, Ruiz-Palacios G, Morrow RC, Butterfoss FD. 1999. Efficacy of home-based peer counselling to promote exclusive breastfeeding: a randomised controlled trial. Lancet 353(9160):1226–1231.

Mulholland K. 1998. Serious infections in young infants in developing countries. Vaccine 16(14–15):1360–1362.

Mulholland K, Suara RO, Siber G, Roberton D, Jaffar S, N’Jie J, Baden L, Thompson C, Anwaruddin R, Dinan L, Glezen WP, Francis N, Fritzell B, Greenwood BM. 1996. Maternal immunization with Haemophilus influenzae type b polysaccharide-tetanus protein conjugate vaccine in The Gambia. Journal of the American Medical Association 275(15):1182–1188.

Musoke RN. 1997. Rational use of antibiotics in neonatal infections. East African Medical Journal 74(3):147–150.

Musoke RN, Revathi G. 2000. Emergence of multidrug-resistant gram-negative organisms in a neonatal unit and the therapeutic implications. Journal of Tropical Pediatrics 46(2):86–91.


Narayanan I, Prakash K, Murthy NS, Gujral VV. 1984. Randomised controlled trial of effect of raw and holder pasteurised human milk and of formula supplements on incidence of neonatal infection. Lancet 2(8412):1111–1113.

Nathoo KJ, Chimbira TH, Mtimavalye LA. 1990. Mortality and immediate morbidity in term babies with low Apgar scores (Zimbabwe). Annals of Tropical Paediatrics 10(3):239–244.

National Institutes of Health, Office of Medical Applications of Research, National Heart, Lung, and Blood Institute, National Institute of Nursing Research. 1994. Consensus Development Conference on the Effect of Corticosteroids for Fetal Maturation on Perinatal Outcomes: Report of the Consensus Development Conference on the Effect of Corticosteroids for Fetal Maturation on Perinatal Outcomes. Bethesda, MD: U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of Child Health and Human Development.


Obaro SK. 2000. Prospects for pneumococcal vaccination in African children. Acta Tropica 75(2):141–153.

Obaro SK, Huo Z, Banya WA, Henderson DC, Monteil MC, Leach A, Greenwood BM. 1997. A glycoprotein pneumococcal conjugate vaccine primes for antibody responses to a pneumococcal polysaccharide vaccine in Gambian children. Pediatric Infectious Disease Journal 16(12):1135–1140.


Palme-Kilander C. 1992. Methods of resuscitation in low-Apgar-score newborn infants—a national survey. Acta Paediatrica 81(10):739–744.

Pan American Health Organization (PAHO). 1999. Respiratory Infections in Children. Benguigui Y, López Antuñano FJ, Schmunis G, Yunes J (eds). Washington, DC: PAHO.

Parashar UD, Bennet JV, Boring JR, Hlady WG. 1998a. Tropical antimicrobials applied to the umbilical cord stump: a new intervention against neonatal tetanus. International Journal of Epidemiology 27(5):904–908.

Parashar UD, Bresee JS, Gentsch JR, Glass RI. 1998b. Rotavirus. Emerging Infectious Diseases 4(4):561–570.

Paul VK, Singh M, Sundaram KR, Deorari AK. 1997. Correlates of mortality among hospital-born neonates with birth asphyxia. National Medical Journal of India 10(2):54–57.

Perchère JC. 2001. Patients’ interviews and misuse of antibiotics. Clinical Infectious Diseases 33(suppl 3):S170–S173.

Phillips I. 2001. Prudent use of antibiotics: are our expectations justified? Clinical Infectious Diseases 33(suppl 3):S130–S132.

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
×

Pillay T, Khan T, Moodley J, Adhikari M, Padayatchi N, Naicker V, Pillay DG, Coovadia HM, 2001. The increasing burden of tuberculosis in pregnant women, newborns and infants under 6 months of age in Durban, KwaZulu-Natal. South African Medical Journal 91(11):983–987.

Prober CG, Hensleigh PA, Boucher FD, Yasukawa LL, Au DS, Arvin AM. 1988. Use of routine viral cultures at delivery to identify neonates exposed to herpes simplex virus. New England Journal of Medicine 318(14):887–891.


Queenan, JT. 2002. Rh-disease: a perinatal success story. Obstetrics and Gynecology 100(3):405–406.

Quiroga R, Halkyer P, Gil F, Nelson C, Kristensen D. 1998. A prefilled injection device for outreach tetanus immunization by Bolivian traditional birth attendants. Revista Panamericana de Salud Pública 4(1):20–25.


Rao RS, Chakladar BK, Nair NS, Kutty PR, Acharya D, Bhat V, Chandrasekhar S, Rodrigues VC, Kumar P, Nagaraj K, Prasad KN, Krishnan L. 1996. Influence of parental literacy and socio-economic status on infant mortality. Indian Journal of Pediatrics 63(6):795–800.

Rawstron SA, Bromberg K, Hammerschlag MR. 1993. STDs in children: syphilis and gonorrhea. Genitourinary medicine 69:(66–75).

Reish O, Ashkenazi S, Naor N, Samra Z, Merlob P. 1993. An outbreak of multiresistant Klebsiella in a neonatal intensive care unit. Journal Hospital Infection 25(4):287–291.

Rice AL, Stoltzfus RJ, de Francisco A, Chakraborty J, Kjolhede CL, Wahed MA. 1999. Maternal vitamin A or β-carotene supplementation in lactating Bangladeshi women benefits mothers and infants but does not prevent subclinical deficiency. Journal of Nurition 129:356–365.

Roberts SW, Cox SM, Dax J, Wendel GD Jr, Leveno KJ. 1995. Genital herpes during pregnancy: no lesions, no cesarean. Obstetrics and Gynecology 85(2):261–264.

Rotchford K, Lombard C, Zuma K, Wilkinson D. 2000. Impact on perinatal mortality of missed opportunities to treat maternal syphilis in rural South Africa: baseline results from a clinic randomized controlled trial. Tropical Medicine and International Health 5(11):800–804.

Rutstein SO. 2000. Factors associated with trends in infant and child mortality in developing countries during the 1990s. Bulletin of the World Health Organization 78(10):1256–1270.


Sachdev HP, Kumar S, Singh KK, Puri RK. 1991. Does breastfeeding influence mortality in children hospitalized with diarrhoea? Journal of Tropical Pediatrics 37(6):275–279.

Sanchez PJ, Wendel GD, Norgard MV. 1991. Congenital syphilis associated with negative results of maternal serologic tests at delivery. American Journal of Diseases of Children 145(9):967–969.

Saugstad OD. 1998. Resuscitation with room-air or oxygen supplementation. Clinical Perinatology 25(3):741–756, xi.

Saugstad OD, Rootwelt T, Aalen O. 1998. Resuscitation of asphyxiated newborn infants with room air or oxygen: an international controlled trial: the Resair 2 study. Pediatrics 102(1):E1.

Save the Children. 2001. Making the Case. In: State of the World’s Newborns: a Report from Saving Newborn Lives. Available online at www.savethechildren.org/mothers/newborns.

Schmid GP. 1996. Serologic screening for syphilis. Rationale, cost, and realpolitik. Sexually Transmitted Diseases 23(1):45–50.

Schuchat A. 1998. Epidemiology of group B streptococcal disease in the United States: shifting paradigms. Clinical Microbiological Reviews 11(3):497–513.

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
×

Schuchat A, Zywicki SS, Dinsmoor MJ, Mercer B, Romaguera J, O’Sullivan MJ, Patel D, Peters MT, Stoll B, Levine OS. 2000. Risk factors and opportunities for prevention of early-onset neonatal sepsis: a multicenter case-control study. Pediatrics 105(1 Pt 1):21–26.

Seaward PG, Hannah ME, Myhr TL, Farine D, Ohlsson A, Wang EE, Haque K, Weston JA, Hewson SA, Ohel G, Hodnett ED. 1997. International multicentre Term Prelabor Rupture of Membrane Study: evaluation of predictors of clinical chorioamnionitis and postpartum fever in patents with prelabor rupture of membra at term. American Journal of Obstetrics and Gynecology 177(5):1024–1029.

Sehgal V, Sethi GR, Sachdev HP, Satyanarayana L. 1997. Predictors of mortality in subjects hospitalized with acute lower respiratory tract infections. Indian Pediatrics 34(3):213–219.

Setia S, Villaveces A, Dhillon P, Mueller BA. 2002. Neonatal jaundice in Asian, white, and mixed-race infants. Archives of Pediatrics and Adolescent Medicine 156(3):276–279.

Shahid NS, Steinhoff MC, Hoque SS, Begum T, Thompson C, Siber GR. 1995. Serum, breast milk, and infant antibody after maternal immunisation with pneumococcal vaccine. Lancet 346(8985):1252–1257.

Shinefield H, Black S, Ray P, Fireman B, Schwalbe J, Lewis E. 2002. Efficacy, immunogenicity and safety of heptavalent pneumococcal conjugate vaccine in low birth weight and preterm infants. Pediatric Infectious Disease Journal 21(3):182–186.

Sikorski J, Renfrew MJ. 2001. Support for breastfeeding mothers. Cochrane Database of Systematic Reviews, Issue 2.

Simkiss DE. 1999. Kangaroo Mother Care. Journal of Tropical Pediatrics 45:192–194.

Singh J, Datta KK, Foster SO. 1997. Sensitivity of neonatal tetanus surveillance system in India. Indian Pediatrics 34(5):398–401.

Smaill F. 2003. Antibiotics for asymptomatic bacteriuria in pregnancy (Cochrane Review). The Cochrane Library, Issue 1.

Smith, R. 2000. Vaccines and medicines for the world’s poorest: public-private partnerships seem to be essential. British Medical Journal 320(7240):952–953.

Snyder JD, Merson MH. 1982. The magnitude of the global problem of acute diarrhoeal disease: a review of active surveillance data. Bulletin of the World Health Organization 60(4):605–613.

Srivastava SP, Sharma VK, Jha SP. 1994. Mortality patterns in breast versus artificially fed term babies in early infancy: a longitudinal study. Indian Pediatrics 31(11):1393–1396.

Starke JR. 1997. Tuberculosis: an old disease but a new threat to the mother, fetus, and neonate. Clinics in Perinatology 24(1):107–127.

Steketee RW, Wirima JJ, Hightower AW, Slutsker L, Heymann DL, Breman JG. 1996. The effect of malaria and malaria prevention in pregnancy on offspring birthweight, prematurity, and IUGR in rural Malawi. American Journal of Tropical Medicine and Hygiene 55:33–41.

Stoll BJ. 1994. Congenital syphilis: evaluation and management of neonates born to mothers with reactive serologic tests for syphilis. Pediatric Infectious Disease Journal 13:845–853.

Stoll BJ. 1997. The global impact of neonatal infection. Clinical Perinatology 24(1):1–21.

Stoll BJ. 2000. Neonatal infections: a global perspective. In: Remington J, Klein J (eds). Infectious Diseases of the Fetus and Newborn Infant. Philadelphia: W.B. Saunders.

Stoll BJ, Measham AR. 2001. Children can’t wait: improving the future for the world’s poorest infants. Journal of Pediatrics 139(5):729–733.

Stoll BJ, Lee FK, Larsen S, Hale E, Schwartz D, Rice RJ, Ashby R, Holmes R, Nahmias AJ. 1993. Clinical and serologic evaluation of neonates for congenital syphilis: a continuing diagnostic dilemma. Journal of Infectious Disease 167(5):1093–1099.

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
×

Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, Ehrenkranz RA, Lemons JA, Donovan EF, Stark AR, Tyson JE, Oh W, Bauer CR, Korones SB, Shankaran S, Laptook AR, Stevenson DK, Papile LA, Poole WK. 2002a. Changes in pathogens causing early-onset sepsis in very-low-birth-weight infants. New England Journal of Medicine 347(4):240–247.

Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, Ehrenkranz RA, Lemons JA, Donovan EF, Stark AR, Tyson JE, Oh W, Bauer CR, Korones SB, Shankaran S, Laptook AR, Stevenson DK, Papile LA, Poole WK. 2002b. Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics 110(2 Pt 1):285–291.

Stoltzfus RJ, Hakimi M, Miller KW, Rasmussen KM, Dawiesah S, Habicht JP, Dibley MJ. 1993. High dose vitamin A supplementation of breast-feeding Indonesian mothers: effects on the vitamin A status of mother and infant. The Journal of Nutrition 123(4):666–675.

Sturm AW, Wilkinson D, Ndovela N, Bowen S, Connolly C. 1998. Pregnant women as a reservoir of undetected sexually transmitted diseases in rural South Africa: implications for disease control. American Journal of Public Health 88(8):1243–1245.


Tafari N, Olsson EE. 1973. Neonatal cold injury in the tropics. Ethiopian Medical Journal 11(1):57–65.

Talukdar B, Rath B, Puri RK, Sachdev HP. 1994. Neonatal tetanus despite antenatal immunization. Indian Pediatrics 31(6):724–725.

Tan BP, Hannah ME. 2001. Oxytocin for prelabour rupture of membranes at or near term. The Cochrane Database of Systematic Reviews, Issue 2.

Terra de Souza AC, Peterson KE, Andrade FM, Gardner J, Ascherio A. 2000. Circumstances of post-neonatal deaths in Ceara, Northeast Brazil: mothers’ health care-seeking behaviors during their infants’ fatal illness. Social Science and Medicine 51(11):1675–1693.

Tessema T. 1994. Risk factors for the development of diarrhoea in the neonatal ward of Ethio-Swedish Children’s Hospital. East African Medical Journal 71(6):384–387.

Thillagavathie P. 2000. Current issues in maternal and perinatal tuberculosis: impact of the HIV-1 epidemic. Seminars in Neonatology 5(3):189–196.

Thorson A, Diwan V. 2001. Gender inequalities in tuberculosis: aspects of infection, notification rates, and compliance. Current Opinion in Pulmonary Medicine 7:165–169.

Tookey P, Peckham CS. 1996. Neonatal herpes simplex virus infection in the British Isles. Paediatric and Perinatal Epidemiology 10(4):432–442.

Traverso HP, Kamil S, Rahim H, Samadi AR, Boring JR, Bennett JV. 1991. A reassessment of risk factors for neonatal tetanus. Bulletin of the World Health Organization 69(5):573–579.

Tulloch J. 1999. Integrated approach to child health in developing countries. Lancet 354(suppl 2):SII16–SII20.


United Nations Children’s Fund (UNICEF). 1999. The Progress of Nations 1999. New York: UNICEF. Available online at www.unicef.org/pubsgen/pon99/index.html.

United Nations Children’s Fund (UNICEF). 2000. Tuberculosis now a global threat. Available online at www.unicef.org/newsline/00pr24.htm.

United Nations Children’s Fund (UNICEF). 2002. The State of the World’s Children 2002. New York: UNICEF. Available online at www.unicef.org/sowc02/fullreport.htm.


van den Broek NR, Letsky EA. 2000. Etiology of anemia in pregnancy in south Malawi. American Journal of Clinical Nutrition 72(1 suppl):247S–256S.

van Ginneken JK, Lob-Levyt J, Gove S. 1996. Potential interventions for preventing pneumonia among young children in developing countries: promoting maternal education. Tropical Medicine and International Health 1(3):283–294.

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
×

Victora CG, Smith PG, Vaughan JP, Nobre LC, Lombardi C, Teixeira AM, Fuchs SM, Moreira LB, Gigante LP, Barros FC. 1987. Evidence for protection by breast-feeding against infant deaths from infectious diseases in Brazil. Lancet 2(8554):319–322.

Victora CG, Smith PG, Vaughan JP, Nobre LC, Lombardi C, Teixeira AM, Fuchs SC, Moreira LB, Gigante LP, Barros FC. 1989. Infant feeding and deaths due to diarrhea. A case-control study. American Journal of Epidemiology 129(5):1032–1041.

Victora CG, Huttly SR, Barros FC, Lombardi C, Vaughan JP. 1992. Maternal education in relation to early and late child health outcomes: findings from a Brazilian cohort study. Social Science Medicine 34(8):899–905.

Victora CG, Kirkwood BR, Ashworth A, Black RE, Rogers S, Sazawal S, Campbell H, Gove S. 1999. Potential interventions for the prevention of childhood pneumonia in developing countries: improving nutrition. American Journal of Clinical Nutrition 70(3):309–320.

Villar J, Bergsjo P. 1997. Scientific basis for the content of routine antenatal care. I. Philosophy, recent studies, and power to eliminate or alleviate adverse maternal outcomes. Acta Obstetricia et Gynecologica Scandinavica 76(1):1–14.

Villar J, Ba’aqeel H, Piaggio G, Lumbiganon P, Miguel Belizan J, Farnot U, Al-Mazrou Y, Carroli G, Pinol A, Donner A, Langer A, Nigenda G, Mugford M, Fox-Rushby J, Hutton G, Bergsjo P, Bakketeig L, Berendes H, Garcia J, WHO Antenatal Care Trial Research Group. 2001. WHO antenatal care randomised trial for the evaluation of a new model of routine antenatal care. Lancet 357(9268):1551–1564.


Weber DM, Freeman NV, Elhag KM. 2001 Periumbilical necrotizing fasciitis in the newborn. European Journal of Pediatric Surgery 11(2):86–91.

Whitley R, Arvin A, Prober C, Corey L, Burchett S, Plotkin S, Starr S, Jacobs R, Powell D, Nahmias A. 1991. Predictors of morbidity and mortality in neonates with herpes simplex virus infections. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. New England Journal of Medicine 324(7):450–454.

Wilkinson D, Sach M. 1998. Improved treatment of syphilis among pregnant women through on-site testing: an intervention study in rural South Africa. Transactions of the Royal Society of Tropical Medicine and Hygiene 92(3):348.

Williams RJ. 2001. Globalization of antimicrobial resistance: epidemiological challenges. Clinical Infectious Diseases 33(suppl 3):S116–S137.

World Bank. 1993. World Development Report 1993. Investing in Health. New York: Oxford University Press.

World Health Organization (WHO). 1991. Safe Motherhood: Maternal and Perinatal Infections: A Practical Guide. Report of a WHO Consultation. Geneva: WHO.

World Health Organization (WHO). 1994. WHO Mother-Baby Package: Implementing Safe Motherhood in Countries. Geneva: WHO. Available online at http://www.who.int/reproductive-health/publications/MSM_94_11/MSM_94_11_table_of_contents.en.html.

World Health Organization (WHO). 1995. Nutrition: information and attitudes among health personnel about early infant-feeding practices. Weekly Epidemiological Record 70:117–120.

World Health Organization (WHO). 1996a. Antenatal Care: Report of a Technical Working Group, Geneva, 31 October–4 November 1994. Geneva: WHO. Available online at http://www.who.int/reproductive-health/publications/MSM_96_8/MSM_96_8_table_of_contents.en.html.

World Health Organization (WHO). 1996b. Perinatal Mortality: A Listing of Available Information. Geneva: WHO.

World Health Organization (WHO). 1996c. Essential Newborn Care. Geneva: WHO. Available at http://www.who.int/reproductive-health/publications/MSM_96_13/MSM_96_13_table_of_contents_en.html.

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
×

World Health Organization (WHO). 1999a. Neonatal Tetanus: Progress Towards Global Elimination, 1990–1997. Web Page. Available online at http://www.who.int/vaccines-diseases/diseases/NeonatalTetanus.shtml.

World Health Organization (WHO). 1999b. Integrated Management of Childhood Illness (IMCI): Management of Childhood Illness in Developing Countries: Rationale for an Integrated Strategy. Geneva: WHO. Available online at http://www.who.int/child-adolescent-health/New_Publications/IMCI/WHO_CHS_CAH_98.1/Rev99.A.pdf.

World Health Organization (WHO) Collaborative Study Team. 2000. Effect of breastfeeding on infant and child mortality due to infectious diseases in less developed countries: a pooled analysis. WHO Collaborative Study Team on the Role of Breastfeeding on the Prevention of Infant Mortality. Lancet 355(9202):451–455.

World Health Organization (WHO). 2001. Guidelines for the Management of Sexually Transmitted Infections. Geneva: WHO. Available online at http://www.who.int/docstore/hiv/STIManagemntguidelines/who_hiv_aids_2001.01.pdf.

World Health Organization (WHO). 2002. Hepatitis B. Web Page. Available online at http://www.who.int/vaccines-diseases/diseases/hepatitis_b.shtml.

World Health Organization (WHO) Young Infants Study Group. 1999a. Bacterial Etiology of Serious Infections in Young Infants in Developing Countries: Results of a Multicenter Study. Geneva: WHO.

World Health Organization (WHO) Young Infants Study Group. 1999b. Clinical Prediction of Serious Bacterial Infection in Young Infants in Developing Countries. Geneva: WHO.


Yamauchi Y, Yamanouchi I. 1990. Breast-feeding frequency during the first 24 hours after birth in full-term neonates. Pediatrics 86(2):171–175.

Yankauer A. 1991. Epidemic diarrhea of the newborn, a nosocomial problem in developing countries. American Journal of Public Health 81(4):415–417.

Suggested Citation:"3. Reducing Neonatal Mortality and Morbidity." Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10841.
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Birth outcomes have improved dramatically worldwide in the past 40 years. Yet there is still a large gap between the outcomes in developing and developed countries. This book addresses the steps needed to reduce that gap. It reviews the available statistics of low birth weight, prematurity, and birth defects; reviews current knowledge and practices of a healthy pregnancy, identifies cost-effective opportunities for improving birth outcomes and supporting families with an infant handicapped by birth problems, and recommens priority research, capacity building, and institutional and global efforts to reduce adverse birth outcomes in developing countries. The committee has based its study on data and information from several developing countries, and provides recommendations that can assist the March of Dimes, Centers for Disease Control and Prevention, and NIH in tailoring their international program and forging new partnerships to reduce the mortality and morbidity associated with adverse birth outcomes.

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