History and Epidemiology

Mary Ellen Avery and Douglas Richardson

EARLY HISTORY OF CARE OF INFANTS*

    In the late nineteenth century and the early part of the twentieth century, deaths from infectious diseases in the first years of life were so common that it is not surprising to find so few students of premature birth and so few articles concerning the special needs of low-birth-weight infants. These small infants were not expected to live. In fact, in the 1940s, some authorities thought of birth weights under 3 pounds as incompatible with life, although rare exceptions have always been noted, as in the case of the Dionne quintuplets, each of whom weighed under 3 pounds. Dafoe, who delivered them on May 28, 1934, wrote, ‘‘There were no scales small enough to measure accurately the separate weights of the babies, but on May 29 [second day] their combined weight was 13 pounds 6 ounces.’’ They were born about 2 months early. Marie, the smallest, weighed 1 1/2 pounds. Yvonne, the largest, weighed nearly 3 pounds. (Accurate scales arrived on the 6th day.)
    As many infectious diseases came under control, physicians turned more attention to newborn infants. It is believed that Budin in Paris published one of the first articles on premature infants in 1888. At about the same time, German physicians, one of whom was Finkelstein in Berlin, became interested in the problems of premature infants and initiated special programs for their care. In Helsinki in 1912, Ylppo pioneered the research on prenatal and postnatal growth and the pathology of prematurity. Hess, an American physician who studied in Europe, was the founder of the first center in the United States that specialized in the care of premature infants; it was established at Michael Reese Hospital in Chicago in 1922. The criterion of 2500 g (5 1/2 pounds) birth weight was used to distinguish a premature from a term infant, and not until much later was the concept of gestational age widely accepted as being a more accurate measure of the stage of development of an infant than weight alone. Physicians who were first concerned with premature infants noted early that these children were unable to maintain their own body temperatures. Various devices, including double-walled metal tubs with the space between the walls filled with circulating hot water, were in use in Europe and Russia in the mid- nineteenth century. Other devices, such as hot-water bottles and electrically heated cribs, were the predecessors of more modern incubators. Occasionally the whole room in which many infants were cared for was kept at high temperatures, paving the way for the modern requirements that constant year-round temperature and humidity be maintained in nurseries where premature infants are cared for.
    It is not surprising that much attention was focused on ways to feed immature infants, particularly because some of them were too weak to suckle. Tarnier is credited with introducing the practice of tube feeding for premature infants at the Maternity Hospital in Paris in 1884. Many other devices for oral and nasal feeding of premature infants have been advocated, but it wasn’t until the 1980s that research made total intravenous nutrition possible.
    The first physicians to care for premature infants considered human milk indispensable for the infants’ welfare. In fact, in 1828, Meissner in Leipzig, Germany, was so convinced of the benefits of human milk that he advised that the infant be fed mother’s milk and be given enemas of milk and at least two milk baths daily.
    A number of physicians, puzzled by the inability of many infants to tolerate cow’s milk, proceeded to compare the chemical composition of human milk and cow’s milk, with the expectation that they could modify cow’s milk to make it a suitable substitute for mother’s milk. In this regard, a number of extreme views were taken, including the idea that cow’s milk contained an indigestible protein, casein, and that diluting it with 3 or 4 parts of water to keep the protein under 1% would improve the infant’s tolerance to this formula. Later it was believed that a higher percentage of protein was necessary to support adequate growth. Over subsequent years, many pediatricians have continued the quest for optimal nutrition for infants of different gestational ages and birth weights, but no universal recommendations have emerged.
    Some early students of the care of premature infants recognized that any epidemic of respiratory tract infection and diarrheal disease could be lethal among such infants. In fact, special units for the care of premature infants were established to avoid the dangers of acquired infection and epidemics within nurseries by providing separate facilities from other patients who might bring infection to the infants. In the early 1900s, guidelines for the care of premature infants specified that incubators that could be easily disinfected should be constructed, that rooms should not be crowded, that personnel should wear gowns and should wash their hands before handling an infant, and that infants with infections should be isolated from other infants.
    It was not until after World War II that a new generation of pediatricians focused their attention on the medical needs of premature infants and, working with pathologists, began to study systematically the causes of death that occurs immediately after birth. Examination of the infants after death showed that not infrequently their lungs were airless, and when examined microscopically they revealed a material, hyaline membrane, in the terminal air spaces that should not have been there. From this discovery, the condition was named hyaline membrane disease; thereafter, the label respiratory distress syndrome was applied to describe the outstanding clinical feature of the disorder. The first obvious assumption was that the material in the lungs was aspirated from the amniotic fluid, but the absence of it in the lungs of infants who were stillborn made that an improbable explanation. Miller made this point in an article in 1949, suggesting that the affected infants acquired the membranes postnatally. Thereafter, many pathologists and pediatricians, through careful study of the infants during their first 2 or 3 days of life and examination of the infants’ lungs after death, clarified this condition as a functional immaturity of the lung with respect to synthesis of pulmonary surfactants. Because of improved understanding, deaths from hyaline membrane disease have decreased from about 10,000 per year in the United States in the 1950s to about 2000 per year in 1994.
    Meanwhile, the 1940s were marked by the construction of many new nurseries and the introduction of more modern incubators that increased the amount of oxygen in the infants’ environment. At that time, it was evident that some of the infants had a newly recognized eye condition, called retrolental fibroplasia, which by the late 1940s became the leading cause of blindness in the United States. The epidemic of this new condition led to enormous speculation about its origin and to a number of studies that culminated in the work by Ashton in England and Patz in Washington. When they exposed kittens to environments containing high levels of oxygen, the kittens acquired the condition. Although oxygen undoubtedly plays a role in retrolental fibroplasia, more recent experience with very immature infants indicates that other as yet undefined circumstances contribute to its severity.
    Increased attention to the needs of small infants resulted in a gradual reduction in their mortality. As more very small infants lived, new problems came into focus. Some could be defined for the first time because of the availability of chemical techniques that allowed measurements on small samples of blood. The application of these newer methods of measurement permitted study of the physiologic adaptations of the infant to extrauterine life. Parallel to increased attention to the infants themselves was the evolution of a field of perinatal physiology, stimulated largely through the work of Barcroft and colleagues in England in the 1930s and 1940s and subsequently by many of their students and colleagues in the 1950s and thereafter.The Physiology of the Newborn Infant by Smith brought many of these observations to the attention of pediatricians in 1945 and again in the three subsequent editions of his classic text.
    The fetal lamb became the experimental model because the animal could be delivered from the uterus with umbilical cord intact and continue to receive oxygen and remove carbon dioxide across the placenta, since the uterus of the ewe does not contract under these circumstances. More recently, it has been possible to place catheters in vessels in the fetal lamb in the uterus for more physiologic studies of fetal life. The events surrounding delivery could then be witnessed in a carefully controlled manner with suitable measurements made to define qualitatively and quantitatively changes in the heart and lungs at birth. From these studies, many suggestions emerged for less direct measurements on the infants that were possible without jeopardizing their condition.
[[*Portions of this chapter appeared in Avery ME, Litwack G: Born Early. Boston, Little, Brown, 1983.]]

RAPID ADVANCES IN NEONATAL CARE: SCIENTIFIC AND TECHNICAL FOUNDATIONS (1955-1970)

    The first edition of Diseases of the Newborn, which was published in 1960, presented the observations of Schaffer and a few colleagues in diagnosis and management of newborn infants and, in so doing, provided a description of the state of neonatology in the late 1950s and stimulated another generation to try to augment the scientific base of a new subspecialty that had long been relatively neglected in medical research and education. Consider for example that neonatal mortality was 20.5/1000 live births in 1950 compared with 7.5/1000 live births in the United States in 1985, 5.4/1000 live births in 1993, and 4.8/1000 live births in 1995.
    The major diagnostic tools in the 1960s were cultures, blood counts, urinalyses, radiographs, and biopsies. Little was known of the pathophysiology of many major disorders of infancy. Pulmonary hyaline membrane syndrome of the newborn was diagnosed by chest film and follow-up of clinical course. Surfactant deficiency, described the year before (1959), was not sufficiently recognized to warrant much discussion in the early 1960s. Blood gases were not available, respirators were not used, and half the infants in whom the diagnosis was made died.
    Mother’s milk was recommended for term infants, but if the mother did not wish to nurse her infant, she was assured the baby would thrive on evaporated milk diluted with water (2 parts to 3), with 5% to 10% added carbohydrate. Premature infants had been observed to have fat intolerance and hence were given half-skimmed milk with added carbohydrate to achieve an average intake of 120 cal/kg per day. Little discussion related to infants smaller than 1300 g (3 pounds) because only 28% survived in 1954.
    In the early 1960s, serial amino acid measurements in the blood of the infants receiving the accepted half- skimmed milk formula revealed transient elevations of phenylalanine and tyrosine that could be damaging to the developing brain. Banking of breast milk, which was common in the 1950s, was markedly decreased when formulas of modified cow’s milk became available. Breast-milk banks have little chance of reappearing now that it is known that viruses can be transmitted by breast milk, and infants without maternal antibody protection can become infected.
    This level of active research attracted a larger number of young clinicians into the special care units, where they began to apply their evolving knowledge of the fetus and newborn. This resulted in the use of intravenous glucose and bicarbonate, blood gas analysis, and improved incubators. Early attempts at mechanical ventilation had dismal outcomes, but any survivors were considered evidence of success.

EMERGENCE OF NEONATAL INTENSIVE CARE (1971-1989)

    A clinical breakthrough in neonatal care was the introduction of continuous positive airway pressure (CPAP) by Gregory and associates (1971). This technique had a powerful and immediate effect on the survival of sick premature infants, but it required around-the-clock care by specialized physicians and nurses. This spurred development of neonatal intensive care units and the impetus to transfer sick newborns from community hospitals to such centers of newborn expertise. CPAP was soon successfully incorporated into strategies for mechanical ventilation that led to design of new ventilators specifically for newborns. The evolution of newborn intensive care required microchemical determinations that permitted controlled intravenous alimentation, devices to measure blood gases, and devices to monitor pulse, respiration, and blood pressure. The rapid influx of pediatricians specializing in newborn care led to the development of fellowships and subspecialty certification in neonatology. Nursing specialization developed concomitantly with a mission not only to provide care to the infants but also to be interactive with and supportive of the infants’ families.
    The advances in survival attributable to neonatal intensive care made it imperative to make intensive care unit services available to a wider population. Initially, this took the form of professionalizing the emergency transport of sick newborns from community hospitals to regional centers using skilled physician/nurse teams dispatched from neonatal centers. In a regionalized system, all hospitals are designated by level according to the intensity of obstetric and neonatal services they provide, including level I (normal birthing and newborn care); level II (common obstetric complications and intermediate newborn care); and level III (around-the-clock high-risk maternal care and intensive care for newborns, including subspecialty and surgical services). Regionalization also included the coordinated movement of patients between hospitals as their needs changed. Bed planning was undertaken on a regionwide basis to provide one level III bed and four to six level II beds per 1000 births. Other components of regionalization included outreach education to the community hospitals, uniform medical records, and standardized statistical reporting for the region. Although regionalization progressed differently in various areas of the United States, overall it had a major impact on reducing neonatal mortality (McCormick et al,1985). Central to this success was the emerging practice of transferring high-risk mothers so that an increasing proportion of all very-low-birth-weight infants was born in perinatal centers. This concentration of patients and obstetric expertise, in turn, facilitated the development of the subs- pecialty of maternal-fetal medicine and of an array of new diagnostic and treatment technologies in obstetrics.
    The field of neonatology became well established and emerged as the largest subspecialty within pediatrics. Neonatologists developed their own special areas of research interest, focusing on organ systems, epidemiology, and mobilization of the tools of cellular and molecular biology. This combination of basic science and clinical trials resulted in steady improvements in nutrition, ventilators, diagnostic technologies, catheters, and surgical techniques. In addition, changes in practice evolved from the relative isolation of sick infants to involvement of family members and primary nurses, and to consultations with other concerned members of society, including pediatricians and ethicists.
    With the increasing survival of extremely premature infants came concern about a possible increase in numbers of handicapped survivors. Numerous studies were undertaken to document risk factors and outcomes. These have indicated that the proportion of handicapped infants has not changed, but the larger number of survivors has led to a larger total number of impaired survivors. Large trials have indicated the value of early educational intervention in optimizing longer-term outcomes (McCormick et al,1993), and such developmentally appropriate care is being incorporated into nursery routines.
    Innovations in neonatal anesthesia and surgical techniques have permitted earlier and more decisive intervention for a variety of major congenital anomalies. This has been most dramatic for congenital heart disease. Previously lethal conditions (such as transposition of the great vessels) can be definitively repaired in the newborn period, and others (such as hypoplastic left heart syndrome) can be successfully palliated. Long-term outcomes are improving steadily.
    Extracorporeal membrane oxygenation (ECMO) was developed in the 1980s as a heroic treatment for total but reversible pulmonary failure. Early successes in treating persistent pulmonary hypertension of the newborn and diaphragmatic hernia led to widespread adoption of ECMO before its efficacy was established in randomized trials. Improving early medical treatments and ventilator strategies, and most recently, nitric oxide, have reduced the number of infants who require ECMO in the 1990s.
    The emergence of a competitive health care environment in the 1980s significantly shaped neonatal intensive care in the United States. The ready availability of well- trained neonatologists and nurses and standardized neonatal technologies have facilitated the proliferation of level III centers, which are predominantly suburban and nonacademic. The traditional models of levels of care and regionalization are being replaced by entrepreneurial intensive care units and contract-based networks.

EXPANSION OF CLINICAL TRIALS TO ASSESS THERAPY: SURFACTANT ERA (1980-1996)

    Administration of glucocorticoids to mothers 24 to 48 hours before delivery to accelerate fetal lung maturation was shown to be effective in the early 1970s. Numerous controlled trials confirmed efficacy and safety, but wide acceptance did not occur until the 1990s. Glucocorticoids are not appropriate in the event of precipitous labor or other maternal contraindications. Rapid acceptance of surfactant replacement therapy and the evidence that prenatal glucocorticoids act to ‘‘condition’’ the lung to enhance the effi- cacy of postnatal surfactant replacement have widened the use of both interventions.
    Early successful clinical trials of surfactant replacement led to the globalization of neonatology in Europe, North America, and Japan. The evident clinical successes were followed by clear documentation of reduction of national neonatal mortality rates for respiratory distress syndrome, formerly the leading cause of death of liveborn preterm infants. Surfactant replacement therapy has had a profound impact on neonatal care as it has shifted the emphasis from acute survival to quality of survival. Increasing numbers of extremely premature survivors remain dependent on sophisticated nursing regimens. Nutritional issues are emerging to dominate neonatology along with optimizing developmental interventions, infection control, and environmental regulation.
    The reduction in deaths from prematurity leaves congenital anomalies, asphyxia and meconium aspiration, and persistent pulmonary hypertension in term infants as major remaining challenges. Newer technologies or combinations of treatments indicate promise in early trials, including surfactant replacement, high-frequency oscillators, inhaled nitric oxide, and less invasive venovenous ECMO. The rapid expansion of prenatal diagnosis, made feasible by genetic probes and high-quality ultrasound, has permitted earlier identification, and counseling has facilitated multi- disciplinary planning before birth for correctable anomalies and provided parental options for severe or lethal anomalies. The anticipated promise of fetal surgery remains largely unfulfilled. Neurologic morbidity among premature infants remains a significant problem, and it is the focus of extensive research aimed at preventing intracranial hemorrhage and white matter damage. The most effective strategy remains aggressive use of antenatal corticosteroids that reduce severity of respiratory distress and risk of intraventricular hemorrhage. An increase in retinopathy of prematurity has been related simply to the survival of larger numbers of extremely immature infants. Great variation in outcomes that has been described among centers may represent differences in the antecedent risks (birth weight, race, obstetric events, illness severity) or differences in the successful application of these neonatal intensive care unit technologies. Efforts to identify the most successful treatment strategies are emerging worldwide through the development of neonatal networks and standardized comparisons.
    It has been customary in the conduct of prospective, controlled clinical trials to match the group receiving the intervention with those who receive a placebo. The matching has traditionally been on the basis of birth weight or gestational age (or both) and occasionally, where relevant, race. It has long been apparent that infants of given gestational age can have widely disparate birth weights, and similarly infants of like birth weights may be of different gestational ages. A more valid approach to constructing a comparable control group and in analyzing the results takes into consideration the severity of the illness to be treated. Both Tarnow-Mordi and colleagues (1990) in the United Kingdom and Richardson and coworkers (1993) in the United States have proposed similar scales for assessing the severity of illness as a predictor of neonatal mortality.
    In an evaluation of the score, Richardson and coworkers(1993) showed that birth weight and severity of illness are each powerful independent predictors of neonatal mortality across a broad range of birth weights and that their effects are additive.
    New questions focus on: How small is too small? When is a new treatment too expensive? What is the physician’s responsibility with respect to starting or discontinuing life support systems in the face of major or irreversible medical problems? Attempts to involve the judicial system have not proven fruitful. Most neonatologists choose to individualize difficult decisions in consultation with the most concerned adults, chiefly parents, nurses, and primary care physicians. A consensus is almost always reached. The enormous costs of such infants at the borderline of viability and the increasing cost consciousness of society have led to substantial debate about whether a lower limit of gestational age (e.g., 23 to 24 weeks) can be defined as eligibility for neonatal intensive care. The tension between patient autonomy, the uncertainty of prognosis, and society’s increasing unwillingness to bear the costs will continue over the coming decades.

DEFINITIONS OF TERMS USED IN CARE OF THE NEWBORN

    In a clarification of definitions by the World Health Organization (WHO) in 1974, Dunn wrote, The perinatal period occupies less than 0.5% of the average life span, yet accounts in many countries for more deaths than the next 30 years. With the reduction in infant and childhood mortality, attention is increasingly being focused on the prevention of perinatal mortality.
    The definitions agreed on by a WHO group in 1974 for reporting purposes remain appropriate in the 1990s. The perinatal period extends from the 28th completed week of pregnancy to the 7th day of life. Clearly, some infants survive after only 25 weeks’ gestation, and, in the future, recording of these births and deaths will be appropriate in societies that are prepared to provide intensive care for newborns. Of course, infant deaths also occur after 7 days, and in the United States, neonatal deaths are often defined as deaths that occur within 28 days of birth, or, for local hospital purposes, deaths that occur before discharge from the hospital after preterm birth.
    A reason to maintain the WHO nomenclature for worldwide comparisons relates to the incomplete records available in some societies for very immature infants. Although infants born before 28 weeks’ gestation account for fewer than 1% of live births, careful recording of births and deaths and inclusion in national statistics penalize the countries that have the best reporting.
    Preterm. Preterm is defined as less than 37 completed weeks’, or 259 days’, gestation. The definition is, of course, arbitrary, but it is based on the greater likelihood of conditions associated with immaturity, such as hyaline membrane disease, in the group of infants born before 259 days. For most developed countries, 37 completed weeks of gestation corresponds to a birth weight of 3000 g.
    Stillbirth and Fetal Death. By definition, early fetal death occurs at less than 20 completed weeks of gestation, intermediate fetal death occurs at more than 20 and less than 28 completed weeks, and late fetal death occurs after 28 weeks. The term stillbirth is usually applied to late fetal deaths.
    Live Birth. WHO defines live birth as The complete expulsion or extraction from its mother of a product of conception, irrespective of the duration of pregnancy, which after such separation, breathes or shows any other evidence of life, such as beating of the heart, pulsation of the umbilical cord, or definite movement of voluntary muscles, whether or not the umbilical cord has been cut or the placenta is attached; each product of such a birth is considered liveborn.
    Term. Term defines births that occur from 37 to less than 42 completed weeks, measured from the day of onset of the last normal menstrual period (259 to 293 days, with an average of 280 days).
    Post-Term. Post-term refers to births that occur at 42 or more completed weeks (294 days).
    Early Neonatal Death. Early neonatal death describes the death of a liveborn infant during the first 7 completed days of life.
    Late Neonatal Death. Late neonatal death refers to the death of a liveborn infant after 7 but before 28 completed days of life.
    In-Hospital Death. Although this term is not included in the WHO system, the authors have found that it is useful to record as in-hospital neonatal mortality any death that occurs within a hospital period that is continuous from birth. Therefore, infants who die at 3 to 6 months or later and who have been hospitalized continuously from birth because of complications and chronic disease following respiratory distress syndrome, congenital anomalies, and other conditions are included in this category.

EPIDEMIOLOGY

Changing Social Scene in United States

    Major changes in life-style and family composition affect the number of infants born and their morbidities. In 1900, children younger than 15 years of age were 34% of the population; in 1990, they were only 22%. Life expectancy at birth in 1920 was 54 years and in 1993 was 75.5 years. The number of children per family was only 1.8 in 1985. Births to unmarried mothers were 22.6% of white births and 68% of black births.
    Marital status relates to unintended pregnancies, which, in turn, is a marker for contraceptive failure (Forrest,1994). An unintended pregnancy occurs if it had not been wanted at the time of conception, regardless of whether or not contraception was being used. Among unintended pregnancies there is a distinction between missed timing and unwanted conception. Missed-time conceptions are those that occur among women who at some time intended to be pregnant but not at the time they conceived. An unwanted conception occurs to a woman when she did not want to have any more pregnancies at all.
    A woman can change her attitude with respect to a pregnancy as the pregnancy proceeds. Occasionally an unanticipated pregnancy can result in a much cherished newborn. These definitions are important because unintended pregnancies are far more likely to end in abortion than are intended pregnancies (Brown and Eisenberg, 1995). More than half of all unintended pregnancies end in abortion. These pregnancies are a major contribution to the 1.5 million abortions per year that have been performed for more than a decade. These data highlight the need for improved sex education and more safe and effective means of contraception.
    Other less quantifiable social trends include frequent moves to other locations, often far from grandparents or other relatives. Immigration is increasing and with it considerable poverty and illnesses.
    An increase in multiple-gestation pregnancies has occurred with assisted reproduction techniques (Luke and Keith, 1992). The number of mothers who delivered twins at Brigham and Women’s Hospital, Boston, in 1991 was 221 compared with 146 in 1986. Higher-order multiple gestations increased by 19% per year, to 23 sets in 1990 from 8 sets in 1986 (Callahan et al, 1994). Many of the infants are preterm and require intensive care.
    It is estimated that nearly one fifth of all children in the United States are poor, principally associated with adolescent pregnancies, single-parent households, and race. One third of black children live in a household with less than $14,335 annual income for a family of four, defined as the poverty level. Poverty is one of many risk factors associated with an increase in violence against individuals of all ages. Parenting practices are of crucial importance and provide the pediatrician with the possibility of early recognition and prevention (Rivara and Farrington, 1995).
    A nationally representative survey of use of illicit drugs has revealed the wide use of stimulants and tranquilizers.* Among women in the 15- to 44-year-old age range, almost half have used illicit drugs once in their life, and 2 million have used cocaine, mostly in the form of crack. In the 1992 survey, it was estimated that 17 million women in that age range were smokers, and 2 million drank five or more alcoholic beverages on one or more occasions in the preceding month. An unexpected finding in the survey was that about 70% of women who reported using drugs also reported having been sexually abused before the age of 16. These women were characterized as having poor nutrition, low self-esteem, depression, and, if pregnant, an increased risk of preterm labor. In addition, they had a greater than expected incidence of sexually transmitted diseases.
    From 1981 to 1997, the Centers for Disease Control and Prevention documented more than 488,300 cases of acquired immunodeficiency syndrome (AIDS) among women in the United States. Nearly 70% were related to either the woman’s own injecting drug use or sexual contact with an injecting drug user.
    Despite the wide publicity given to the adverse effects of cigarette smoking and alcohol use during pregnancy, it is estimated that approximately 19% of women used alcohol and 20% smoked cigarettes at some time during pregnancy. The national survey also found that illicit drug use was more prevalent in women who were not married and had had less than 16 years of formal education, were not working, and relied on some public source of funding to pay for their hospital stay.
    These findings underscore the compelling need to consider the health of the mother and the adequacy of her support services whenever efforts are undertaken to reduce the morbidities and mortality of newborn infants.
[[*Data obtained from the National Institute on Drug Abuse, 5600 Fishers Lane, Rockville, MD 20857.]]

Pregnancy Outcomes

The outlook for a successful outcome of pregnancy has improved dramatically (Fig. 1-1 ). A rough chronology of major advances is listed in Table 1-1 . The impact of new knowledge and its application has resulted in an impressive reduction in deaths in the first year of life in the United States, with a 50% reduction in mortality rates from 1970 to 1985 and a 15% reduction in the rate of low-birth- weight infants. Most of the reduction in infant mortality has been attributed to the decline in birth weight-specific mortality, presumably related to improvements in perinatal care. The number of deaths from respiratory distress syndrome and hyaline membrane disease in the United States in four different 5-year periods is shown in Table 1-2 .

Race

    Overall the mortality rate of nonwhite infants in the first year of life is twice as high as that of white infants. The higher rate of preterm births (12.8% in nonwhite compared with 7.4% for whites) was a large factor in the Massachusetts experience reported by Wise and coworkers (1985). The weight-specific mortality is actually lower in black infants weighing less than 2500 g (Table 1-3 ). Infant mortality rates by age and race from 1940 to 1992 are shown in Table 1-4 .
    The reasons for the relative advantage of blacks when they are born prematurely may relate to biologic factors, such as their accelerated lung maturation. The marked disadvantages in the first year of life of black infants born with weights greater than 2000 g are thought to be related to adverse socioeconomic factors (Miller and Jekel, 1987).
    An interval of less than 9 months between pregnancies is associated with a greater prevalence of preterm birth and low birth weight among black women. This observation was seen among white women only with intervals of less than 3 months. An interpregnancy interval of less than 9 months was more than 10 times more common among black women in a study of 1922 women reported by Rawlings and colleagues (1995). This is surely a factor in understanding the continuing wide disparity in pregnancy outcome.

Maternal Age

In general, the best outcome of pregnancy takes place when the mother is over age 20 and under age 35. Extension of maternal age in either direction has generally been thought to result in an increase in infant mortality. Berkowitz and coworkers (1990) have reported that although pregnancy complications are increased, mortality need not be increased in pregnancies of healthy middle-class women. An association between the percentage of mothers under

age 20 years and infant mortality in four countries is shown in Table 1-5 . Because pregnancy among adolescents occurs more commonly among mothers of lower socioeconomic status and more often among nonwhites than whites, assigning relative importance to these and other factors that coexist with young maternal age has been a challenge.
Several reasons are often cited for the rise in teenage pregnancies, principally the growing number of teenagers and the increase in sexual activity. In the United States, more than 900,000 teenage women between ages 15 and 19 become pregnant each year, and almost 25,000 are 15 years old or younger. Adolescent mothers contribute 19% of the births but have 26% of the low-birth-weight infants. These mothers have increased risks for death in childbirth, toxemia, anemia, and neurologic disorders in their offspring. On the average, infants born to adolescent mothers may be less well nurtured, have a greater risk of child abuse, and receive less health supervision as children. Similarly, adolescent mothers who have infants are more prone to marital dissolution and emotional disturbances. Obviously, causes and effects are difficult to unravel, but there is little doubt that for a young woman between 15 and 19 years of age, pregnancy may contribute to what Smith described in 1980 as ‘‘a dismal future of unemployment, poverty, dropping out of school, family breakdowns, emotional stress, dependency on public health agencies, and health problems for mother and child.’’ Pregnancy after age 40 years is associated with another set of hazards for the baby. For pregnant women over 40 years, a sharp increase in deaths around the time of birth (perinatal mortality) occurs with each subsequent year of age. After 40 years of age, the hazards are greater if it is the woman’s first pregnancy rather than a subsequent pregnancy. One of the risks of pregnancy after age 40 years is the approximately 2.6% incidence of Down syndrome in the infant compared with an overall incidence of 0.15%. Another problem relates to diminished elasticity of the pelvic structures, which results in difficulties with delivery and a greater likelihood of preterm labor. Diagnostic amniocentesis for detection of chromosome abnormalities such as Down syndrome can alert the mother to that possibility and provide her with the option of abortion. Skillful obstetric management can reduce these hazards around the time of delivery.

Prenatal Care

Numerous studies have documented the higher incidence of prematurity and growth retardation in infants of mothers from a lower socioeconomic group, and among the findings is a specific association of these developmental problems with lack of prenatal care (Miller and Jekel, 1987; Wise et al, 1985). Many confounding factors complicate the interpretation of these and similar findings. It is not known what aspects of prenatal care have a significant bearing on the outcome of a pregnancy. It seems reasonable to give much credit to health education (Kogan et al, 1994). The mothers who want to do what is best for their babies are

probably the ones who elect prenatal care. Early detection of risk factors, hypertension, and poor or excessive weight gain surely dictates appropriate interventions, which on the whole improve the outcome of pregnancy.

GLOBAL PERSPECTIVES IN THE FUTURE OF NEWBORN CARE

Currently, focus is on the national embarrassment of the relatively high infant mortality rate in the United States compared with other developed nations and the persistently high mortality among nonwhite infants. Goals set in 1979 for the year 1990 were not met and require a concerted federal and state effort to reduce the social and economic barriers to access to prenatal care in the 1990s (Table 1-6 ).
There is increasing worldwide attention to the disparities in infant mortality and the circumstances that are deemed responsible. The lowest rates ever recorded were set in the mid-1980s when Japan achieved an infant mortality

rate of 5.5 per 1000 live births, followed closely by Finland and Sweden, with the United States well behind at 10.6. By 1993, Japan reported a rate of 4.4 per 1000 live births, Sweden 4.8, and the United States 8.3 (Wegman,1994). These so-called developed countries have vastly lower infant mortality rates than most of the countries in the world. According to data collected by the United Nations Children’s Fund in 1992, at least 32 countries reported infant mortality rates of greater than 100 per 1000 live births. These included many of the countries of sub- Saharan Africa, Southeast Asia, and Central and South America.

Maternal Perspectives

    In some societies, the maternal mortality rate is also shockingly high. In the developed countries, the maternal mortality rate is approximately 1 per 10,000 births, whereas among the poorest countries it is more than 100 times as high.
    Priorities must differ in the context of the existing situations in each country. In a careful examination of the problem in the Zaria area of northern Nigeria, Harrison(1985) commented that preventing stillbirths of term infants who died in utero before their mothers arrived at the hospital is the highest priority.
    Although there is recognition that the prevention of low birth weight by preterm delivery is clearly important, the high mortality of normal-birth-weight infants remains the central concern. Among the factors that contribute to the problem are the observation that in a traditional sub-Saharan society, African women are accorded an inferior status. They take a limited part in the decision-making process, even when it involves child-bearing. The decision to transfer a desperately ill pregnant woman to a hospital is nearly always made by the husband, and in his absence

others may be unwilling to make the decision. There is a traditional dislike of operative deliveries, so that even when labor is obstructed, consent to relieve the obstruction by cesarean section may require prolonged discussion. Marriage soon after puberty is widely practiced among the illiterate traditional majority of individuals. Most of the girls of this age are underdeveloped and also nutritionally deprived so that pelvic contraction is common. A further problem is that young primigravidae are often shy about their pregnancies, strive to conceal the fact, and therefore have no prenatal care. Home delivery is nearly always preferred by that particular population.
Although the biosocial issues that have an impact on the outcome of pregnancy are complex, some of the solutions are straightforward. It is fair enough to say that major structural changes in the existing political, economic, and cultural milieu are necessary for major improvements to occur over the long-term. It is also clear that providing facilities for antenatal care and an educational program that promotes their use can make an immediate difference. The development of facilities for performing cesarean sec tion safely has to be a priority, as does the availability of safe blood transfusions.

Pediatric Perspectives

Experiences in developed and developing countries suggest that perinatal mortality may be reduced by 30% to 40% within a few years by the application of some straightforward, commonsense interventions. These include the recognition of risk factors and the identification of women who are likely to have difficulty during the perinatal period so that they may be delivered in safe settings. It also means applying current knowledge, such as ensuring the availability of appropriate resuscitation and thermal environment for an infant, the encouragement of timely breast- feeding, and the minimizing of the risk of infection by making hand-washing a consistent practice. It is extraordinary to realize that in some hospital-based intensive care nurseries or even routine care nurseries, the caretakers move from infant to infant without washing hands between examinations. In many nurseries, no sinks are readily available except those at a considerable distance, and even then they may not be equipped with soap or disposable towels. The high prevalence of nosocomial infection in such environments is not surprising. In fact, the leading cause of death in many such settings is acquired infection in the period after delivery. Encouraging mothers to care for their own infants is, of course, an important intervention to provide where possible and is widely practiced in some of the developing countries. If individuals other than the mother are to care for infants, they must be required to wash their hands; be taught not to insert their fingers into the infants’ mouths; and be encouraged to make sure that sheets, blankets, and other objects with which the infant comes in contact have been washed and preferably sterilized. It is essential to realize that where the infant mortality rate is high, it can be reduced by at least one third, if not one half, through the application of the straightforward caretaking measures just cited.
Clearly major contributions to the reduction in the mortality of both term and low-birth-weight infants that has taken place in the developed countries have been the use of better incubators, temperature control devices, and respirators and the ability to monitor blood gases and to have microchemical determinations promptly available.

Because such advanced equipment and the highly trained personnel to work with it cannot be reproduced in all settings where babies are born, it is inappropriate to assign their availability the highest priority.
Each society must identify its own problems and ascertain the most appropriate, feasible interventions. In 1979, the U.S. Public Health Service defined a list of objectives for 1990, which were not achieved (see Table 1-6 ). Nothing will improve, however, without the advocacy of those who care about the health of mothers and infants in any social context. The remarkable success that has been achieved in the Scandinavian countries and Japan is encouraging. Maternal mortality is almost always preventable, and infant mortality should be less than 5/1000 live births. Fortunately, when infant mortality falls, fertility rates also fall because there is less need for a woman to have multiple pregnancies if there is reasonable assurance of the survival of each infant. This observation has been duplicated in every society in which there has been a reduction in infant mortality, including the United States (Tables 1-7 and 1-8 ). The coupling of efforts to reduce maternal and infant mortality with advice on family planning and child spacing would seem to be the most important goal for the next decades. Universal access to prenatal care is a high priority. Stimulated by the leadership shown by WHO, UNICEF, and the International Pediatric Association as well as local pediatric societies and religious groups, the goals for the year 2000 could be attainable. At least, clinicians should not rest until progress in reaching the goals is seen being made in all parts of the world.

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