National Academies Press: OpenBook

Preventing Low Birthweight (1985)

Chapter: 1. The Significance of Low Birthweight

« Previous: Part I: Definitions, Risk Factors, and Trends
Suggested Citation:"1. The Significance of Low Birthweight." Institute of Medicine. 1985. Preventing Low Birthweight. Washington, DC: The National Academies Press. doi: 10.17226/511.
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Suggested Citation:"1. The Significance of Low Birthweight." Institute of Medicine. 1985. Preventing Low Birthweight. Washington, DC: The National Academies Press. doi: 10.17226/511.
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Suggested Citation:"1. The Significance of Low Birthweight." Institute of Medicine. 1985. Preventing Low Birthweight. Washington, DC: The National Academies Press. doi: 10.17226/511.
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Suggested Citation:"1. The Significance of Low Birthweight." Institute of Medicine. 1985. Preventing Low Birthweight. Washington, DC: The National Academies Press. doi: 10.17226/511.
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Suggested Citation:"1. The Significance of Low Birthweight." Institute of Medicine. 1985. Preventing Low Birthweight. Washington, DC: The National Academies Press. doi: 10.17226/511.
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Suggested Citation:"1. The Significance of Low Birthweight." Institute of Medicine. 1985. Preventing Low Birthweight. Washington, DC: The National Academies Press. doi: 10.17226/511.
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Suggested Citation:"1. The Significance of Low Birthweight." Institute of Medicine. 1985. Preventing Low Birthweight. Washington, DC: The National Academies Press. doi: 10.17226/511.
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Suggested Citation:"1. The Significance of Low Birthweight." Institute of Medicine. 1985. Preventing Low Birthweight. Washington, DC: The National Academies Press. doi: 10.17226/511.
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Suggested Citation:"1. The Significance of Low Birthweight." Institute of Medicine. 1985. Preventing Low Birthweight. Washington, DC: The National Academies Press. doi: 10.17226/511.
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Suggested Citation:"1. The Significance of Low Birthweight." Institute of Medicine. 1985. Preventing Low Birthweight. Washington, DC: The National Academies Press. doi: 10.17226/511.
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Suggested Citation:"1. The Significance of Low Birthweight." Institute of Medicine. 1985. Preventing Low Birthweight. Washington, DC: The National Academies Press. doi: 10.17226/511.
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Suggested Citation:"1. The Significance of Low Birthweight." Institute of Medicine. 1985. Preventing Low Birthweight. Washington, DC: The National Academies Press. doi: 10.17226/511.
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Suggested Citation:"1. The Significance of Low Birthweight." Institute of Medicine. 1985. Preventing Low Birthweight. Washington, DC: The National Academies Press. doi: 10.17226/511.
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Suggested Citation:"1. The Significance of Low Birthweight." Institute of Medicine. 1985. Preventing Low Birthweight. Washington, DC: The National Academies Press. doi: 10.17226/511.
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Suggested Citation:"1. The Significance of Low Birthweight." Institute of Medicine. 1985. Preventing Low Birthweight. Washington, DC: The National Academies Press. doi: 10.17226/511.
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Suggested Citation:"1. The Significance of Low Birthweight." Institute of Medicine. 1985. Preventing Low Birthweight. Washington, DC: The National Academies Press. doi: 10.17226/511.
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Suggested Citation:"1. The Significance of Low Birthweight." Institute of Medicine. 1985. Preventing Low Birthweight. Washington, DC: The National Academies Press. doi: 10.17226/511.
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Suggested Citation:"1. The Significance of Low Birthweight." Institute of Medicine. 1985. Preventing Low Birthweight. Washington, DC: The National Academies Press. doi: 10.17226/511.
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Suggested Citation:"1. The Significance of Low Birthweight." Institute of Medicine. 1985. Preventing Low Birthweight. Washington, DC: The National Academies Press. doi: 10.17226/511.
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Suggested Citation:"1. The Significance of Low Birthweight." Institute of Medicine. 1985. Preventing Low Birthweight. Washington, DC: The National Academies Press. doi: 10.17226/511.
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Suggested Citation:"1. The Significance of Low Birthweight." Institute of Medicine. 1985. Preventing Low Birthweight. Washington, DC: The National Academies Press. doi: 10.17226/511.
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Suggested Citation:"1. The Significance of Low Birthweight." Institute of Medicine. 1985. Preventing Low Birthweight. Washington, DC: The National Academies Press. doi: 10.17226/511.
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Suggested Citation:"1. The Significance of Low Birthweight." Institute of Medicine. 1985. Preventing Low Birthweight. Washington, DC: The National Academies Press. doi: 10.17226/511.
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Suggested Citation:"1. The Significance of Low Birthweight." Institute of Medicine. 1985. Preventing Low Birthweight. Washington, DC: The National Academies Press. doi: 10.17226/511.
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Suggested Citation:"1. The Significance of Low Birthweight." Institute of Medicine. 1985. Preventing Low Birthweight. Washington, DC: The National Academies Press. doi: 10.17226/511.
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CHAPTER 1 The Significance of Low Birthweight The observation that babies born too small are less likely to survive than other newborns dates back centur ies, ~ but concern over the effects of low birthweight on a child ' s health and development is relatively recent. This chapter traces the changes in perspective that have occurred as infant mortality from other causes has declined, and as modern technologies have provided the capability to sustain even the tiniest neonate. It also examines the contribution of low birthweight to morbidity and mortality in general and the need for improved strategies to prevent low birthweight. Although the earliest references to the practice of weighing infants at birth date from Talmudic times, the potential significance of birthweight does not appear to have been recognized until the end of the seventeenth century, when it was discussed by the French obstetrician Mauriceau. Unfortunately, Maur iceau ' s widely c ited measurements were incorrect--his estimate of a normal birthweight was about 15 pounds. A more accurate assessment of normal birthweight did not enter the English literature until late in the eighteenth century. Almost another hundred years passed before systematic weighing of infants at birth revealed sufficient variability in birthweights to support the concept that weight could be used to assess nutritional status and phys ical growth .2 By the early laces, physicians had begun to assess the relationships among inadequate growth (low birthweight), shortened gestation (prematurity), and mortality. In 1930, the Finnish pediatrician, Yllpo, advocated 2,500 -trams as the birthweinht below which infants were at high risk of adverse neonatal outcome, presumably on the basis of inadequate fetal growth.3 This recommendation was formally adopted by the World Health Organization (WHO) on two separate occasions. The first was at the First World Health Assembly in 1948: "For the purpose of this classification, an immature infant is a liveborn infant with a birthweight of 5-1/2 pounds (2,500 grams) or less, or specified as immature. In some countr ies, however, this criterion will not be applicable. If weight is not specified, a liveborn infant with a period of gestation of less than 37 weeks or specified as 'premature' may be considered as the equivalent of an immature infant for purposes of this classification. no _ _ 21

22 In 1950, the WHO Expert Group on Prematurity reinforced the use of the 2,500-gram limit: "The Expert Group on Prematurity recognizes the necessity for uniform terminology for international usage. Since the primary goal is to lower fetal and neonatal mortality, the aim can best be achieved by providing specialized care for infants of low birth- weight. The group suggests that a premature infant be def ined as one whose bi rth-weight is 2 ,500 g O (5-1/2 pounds) or less. The limitations of this or utter ion are recognized, however, since data on birth-weight will not always be available and other criteria of prematurity must be used, for example, gestation. nS Both recommendations indicated that the use of a birthweight marker for risk served as a shorthand notation for a var iety of interrelated physiologic processes affecting fetal growth and duration of gestation. The complexity of the issue was underscored by subsequent epidemio- logical studies, which confirmed that infants born weighing 2 ,500 grams or less were at increased risk of mortality,6 but also showed that a birthweight of 2 ,500 grams was not synonymous with short gestation-- some full-term infants weigh 2,500 grams or less. 7 ~ These observations led to further alar if ication of the def initions by the 1961 WHO Expert Committee on Maternal and Child Health.9 ~° This group recommended that the word "premature" be reserved for infants born before 37 weeks from the f irst day of the last menstrual period. Infants born weighing 2,500 grams or less were now to be considered slow birthweight." The classification was divided further to distinguish between the low birthweight infant (gestation of 37 weeks or longer, birthweight 2 ,500 grams or less) and the premature low birthweight infant (gestation less than 37 weeks, birthweight 2,500 grams or less). The former were considered to be Stunted" for duration of gestation and character ized by different r isks of mortal' ty and morbidity than infants who were premature and whose birthweights were, therefore, more consistent with gestational age. ~ ° While these gestational age/b~rthwe~ght classif ications proved useful in delineating subpopulations of low birthweight infants with different etiologies and prognoses, they posed some of the same ambiguities as birthweight al one: · Birthweight is a continuous variable and the limit at 2,500 grams does not represent a biologic category, but a singl e point on a continuous curve. The infant born at 2,499 grams does not differ significantly from one born at 2,501 grams on the basis of birthweight alone. ~ Although 37 weeks of gestation may reflect biologic processes more directly, because certain biochemical changes indicative of increasing fetal maturity occur about this time, variation is such that not all 37-week infants are equally mature. · The population of infants who weigh 2,500 grams or less and are less than 37 weeks gestat ion is not homogeneous with respect to outcome; further distinctions are required to classify those at increased risk. · The r isk of mortality as it applies to the birthweight/gesta- tional age distribution varies for different populations.

23 With the emergence of modern approaches to the management of low birthweight infants, interest increased in the outcomes of subgroups of low birthweight infants. The fate of the smallest infants was of particular concerned 12 -~ ~~ I_ ~~- =;_~;~- `_~IV=~] ~1~4 ~ y ~ V AL y ~ ~W MEL ~~`y11~ infants were considered to be those born weighing 1,500 grams or less. Even with more specific birthweight categories, it was recognized that infants with similar birthweights could be of different gestational ages. Those whose birthweights were consistent with their gestational ages differed in outcome from those whose birthweights were not (especially when the birthweight was substantially lower than expected) .~3 l. As with Me 2,500-gram ~ imit, designation of very low birthweight infants as those weighing 1,SOO grams or less reflected convention rather than biologic or iter ia. Current Concepts of Fetal Growth Current descr iptions of fetal growth parallel the Growth curve n approach used to descr ibe growth throughout childhood. At any given age (whether in utero or after birth}, most individuals tend to be similar in size and weight, although variation exists. Since the advent~of statistical concepts, particularly that of the "normal distribution, ~ observations incorporating botch similarity among the majority and wide variation are described in terms of "means" and Deviations from the mean." The term ~average" growth refers to the value about which the majority cluster. Thus, the expected birthwe~ght at any given gestational age would be the average or mean birthweight of infants at that gestational age. The definition of abnormal growth requires identification of those whose growth deviates from what would be expected given normal or anticipated variation. Normally distributed data such as weight and other measures of physical growth form smooth curves, which theoretically extend to infinity without clear discontinuities, so ~abnor~lity. is most practically def ined in terms of the likelihood that an individual observation will fall within the normal variation expected for a given population. The lower this probability, the more 1 ikely the individual observation represents an abnormality. Commonly, an ~abnormal" observation is considered to be one that falls outside the range described by two standard deviations on either side of the mean. This range includes 9S percent of a population, so an observation outside that range would have only a 5 percent chance of reflecting normal var. iation. ~ s Application of this approach to the distribution of birthweights in different populations indicates that two standard devi ations below the mean does not always fall at 2 ,500 grams . In fact, one study of birthweights by country showed that two standard deviations below the mean ranged from 1,850 to 2 ,250 grams.3 (The coding of birthweights, i.e., in exact grams, or by 250- or 500-gram intervals, also can affect mean values and standard deviations.3} These observations have been used to argue for different ways of defining high-risk groups to allow more accurate comparisons of birthwe~ght-related infant mortality figurese3 16 17

24 The use of different birthweight limits to designate high-risk subgroups of a population has special relevance in the United States, where an effort has been made to identify racial differences in birthweight distributions. Nonwhite low birthweight infants have lower neonatal mortality rates than white infants of the same birthweight ~9 It has been argued, therefore, that the lower birthweight of nonwhites may reflect prior genetic or nutritional factors but not contribute to current risker and that the 2,500-gram birthweight limit may not have the same implications for nonwhite infants as for whites (i.e., that low birthweight should perhaps be defined differently for nonwhite infants). This line of reasoning is overshadowed by the more imposing fact that nonwhite infants are twice as likely to be born at low birthweight and twice as likely to die in the neonatal period. Chapter 2 discusses race as a risk factor for low birthweight in more detail. Recent publications20 21 on birthweight distributions at different gestational ages have improved the physician's ability to identify preterm infants who have experienced inadequate growth (Figure 1.1~. Growth curves tied to gestational age also allow standardization of terms such as Small for gestational age" and Appropriate for gestational age"; precise definition of these terms is essential for future clinical and ep~demiological studies. In view of the more sophisticated data available, the continued reliance on a single standard, 2,500 grams, as a measure of risk for adverse perinatal outcome could be questioned. The rationale for retaining this standard rests on four arguments. First, although birthweight/gestatzonal age combinations provide useful information, they require accurate assessments of gestational age, which is considerably more difficult to measure than birthweight Second, birthweight appears to be relatively more important in determining prognosis than gestational age. Third, the use of standard birthweight limits allows comparisons across time and populations. Most important, as will be illustrated in the remainder of this chapter, a substantial literature exists to support the use of low birthweight as a marker or risk factor for mortality and morbidity. Birthweight and Infant Mortality The contribution of low birthweight to infant mortality in the United States Is relatively greater now than it was in the past. Support for this assertion is indirect and is based on the fact that two-thirds of infant deaths early in the century occurred in the postneonatal period (between 28 days and 11 months of age).22 Postneonatal deaths are considered a reflection of environmental factors, particularly infections resulting in diarrhea or respiratory illness.22 2 3 In developing countries, where infant mortality rates remain high, low birthweight accounts for less than half (20 to 40 percent) of postneonatal deaths.2 4

25 4500 4000 3500 3000 2500 I CI: ~ 1500 2000 1 000 500 o al {/~//~ 50% 10%— / . 1 1 1 1 1 1 1 1 0 22 26 30 34 38 42 46 WEEKS OF GESTATION COMPLETED FIGURE 1. 1 Bir thweight percentiles for f ixed gestations for single births, California, 1970 to 1976. SOURCE: Williams RL, Creasy RK, Cunningham GC, Hawes WE, Norris FD, and Tashiro M: Fetal growth and perinatal viability in Cal' fornia. Obstet. Gynecol . 59: 624-632, 1982 . Over the first half of the century, infant mortality rates In the United States declined from 100 per 1,000 live births to about 50 per 1,000.25 Most of this decrease occurred among postneonatal deaths, so the majority of observers attribute this decline to changes In the environment, including a reduction in infectious diseases and improved nuts ition.2 2 2 3 2 5 The contr iblltion of shifts in birthweight distribution is unknown, but probably was not significant. Data for the past 30 years reveal relative! y slow changes in birthweight distribution,2 6 suggesting that major shifts probably did not occur in the past.

26 With the reduction in postneonatal mortality, a shift in the timing of infant deaths occurred. By 1950, two-thirds of all infant deaths were in the neonatal period.25 The major causes of these neonatal deaths were antenatal and intrapartum events such as birth injury, asphyxia, congenital malformations, and n immaturity. n2 s As an indicator of the contribution of immaturity, the proportion of i nfants weighing 2,500 grams or less was 7.5 percent in 1950 '2 6 but these infants accounted for two-thirds of neonatal deaths.2 s Recognition of increased morbidity in surviving low birthweigh t infants grew in the 1950s and 196Os. Early studies indicated that low birthweight infants were at increased r isk of neurodevelopmental problems, especially cerebral palay2 7 and seizure disorders.28 This increased vulnerability of low birthweight infants and the nature of some of the etiologic factors that con tr ibuted to their increased risk were established in a study of a large cohort of U.S. births followed prospectively in the Collaborative Perinatal Study.29 30 Reports from other countries3 1 indicated that she n S: "xn~rimnm. =:.c not unique. _ , This growing body of knowledge helped to establish the context for modern perinatal care. Further reductions in infant mortality seemed likely to require solutions to the problems of the neonatal period, especially those related to low birthweight. The two major alternatives in this effort were the prevention of low birthweight in infants and the development of techniques to increase the survivability of low birthweight neonates. The former, which appeared to be more desirable, included efforts to develop early risk assessment programs32 33 and services for high-risk mothers, including those from socioeconom~cally disadvantaged segments of society.3 4 3 5 met ~ ~ ~ - __~ I1le =~:~Vll~l Cal- AL loci ~1-V~: r increasing the survival of low birthweight infants, induced clinicians to develop new management strategies, such as neonatal intensive care units. This approach was associated with the potential disadvantage of an increase in the number of children suffering from handicaps related to antenatal and intrapartum events, especially neurodevelopmental problems. This risk of increased morbidity has led clinicians to evaluate neonatal intensive care not only in terms of survival, but also In terms of developmental outcomes. Since the early 1950s, the proportion of low birthweight infants has declined modestly.26 Recent figures for the United States indicate that 6.8 percent of all neonates weigh 2,500 grams or less. 3 6 Almost no change in the proportion of infants born at very low birthweights (1,500 grams or less) has occurred, and these infants constitute just over 1 percent of all births. Thus, of the 3,494,398 live births in 1979, 252,511 weighed 2,500 grams or less, and 40,186 weighed ~ ,500 grams or less. Assessing the contribution of low b~rthweight infants to mortality in the population requires b~rthweight-spec~f ic mor tality rates der ived from files containing infant death certificates matched to the corresponding birth certificates, as well as morbidity information on surviving children. Unfortunately, such data are not available for the United States as a whole. However, some indirect evidence of an association between low birthweight and mortality on a national level can be gleaned from racial differences in neonatal mortality figures.

27 Infants born to blacks are twice as likely to weigh 2,500 grams or less than those born to whites (12.7 percent versus 5.9 percent); this increased r isk also pertains to the proportion in the lowest birthweight group of 1,500 grams or less (2.4 percent versus 0.9 percent).36 Parallel to this difference in birthweight distribution is a difference in infant mortality. Between 1977 and 1979, the overall infant mortality rate was 13.6 per 1,000 live births, 11.3 for white births and 22.8 for black births.3 6 Black births accounted for 16.5 percent of all live births in this per iod, but for 30 percent of all low birthweight births, 34 percent of very low birthweight births, and 28 percent of infant deaths. More direct estimates of the effect of birthweight on mortality can be der ived from several recent large-scale analyses relying on matched infant death and b ir th f iles . Wh ile these analyses do not deal with the nation as a whole, the results probably can be generalized. The relationship between birthweight and infant mortality has been documented repeatedly in a par iety of settings. ~ 9 - 2 ~ 2 4 2 5 3 ~ 3 7 - 3 9 The lowest mortality rates are exper fenced by infants weighing 3 ,000 to 3 ,500 grams . For infants weighing 2 ,500 grams or less r the mortality rate increases rapidly with decreasing birthweight Most of the infants weighing 1, 000 crams or less die (Figure 1. 2), although among those that live until admission to a neonatal intensive care unit, survival rates are believed to be improving considerably. Compared with normal birthweight infants, low birthweight infants are almost 40 times more likely to die in the neonatal per iod; for very low birthweight infants, the relative r isk* of a neonatal death is almost 200 times greater.~9 Not only are low birthweight infants at increased relative r isle of neonatal mortality, but the attributable risk or proportion of all neonatal deaths occurring among low birthweight infants also is high *In The Risk Approach in Health Care,40 the World Health Organization defines and discusses both relative and attr ibutable r isk. Relative r isk "expresses the ratio between the incidence of the illness or cause . of death [or, in this case, low birthweight in the population of those with the r isk factor (or factors ~ and the correspond) ng incidence in the population of those without the r Ask factor (or factors) . It is therefore a measure of the strength of the association between r isk factor and outcome . . . . Attr ibutable r isle br ings together three ideas: the frequency of the unwanted outcome [here, low birthweight when the risk factor is present, the frequency of the outcome when the r isk factor is absent, and the frequency of occur ence of the r isk factor in the community. It therefore indicates what might be expected to happen to the overall [incidence of the unwanted] outcome in the community if the risk factor were removed" (pp. 21-221. A Ore extensive discussion of the concepts of relative and attributable risk, along with methods for their calculation, appears in Foundations of Epidemiology, by Lilienfeld and Lilienfeld, 2nd Edition. New York: Oxford Univer sity Press, 1980 .

28 1000 800 600 400 _ \ 300 _ )\ 200 Lit * Deaths under 28 days per 1000 live births t Deaths 28 days-11 months per 1000 survivors of neonatal period 100 80 60 40 30 20 10 8 6 4 3 2 \ Neonatal Mortality* Postneonatal \ Mortality ~ \ N\\~ t \~~~~ / I\ t 1 1 1 1 1 1 1 ~1000 1001- 1501- 2001- 2501- 3001- 3501- 4001- ~4501 1 500 2000 2500 3000 3500 4000 4500 BIRTHWEIGHT (grams) FIGURE 1. 2 Neonatal and postneonatal deaths by birthweight, single live births, 1974 to 1975, based on data from eight areas of the United States. SOURCE: Shapiro S. McCormick MC, Star f ield BE, Kr ischer JP, and Bross D: Relevance of correlates of infant deaths for significant morbidity at 1 year of age. Am. J. Obstet. Gynecol. 136: 363-373, 19B0 .

29 (see definition of attr ibutable risk above) . Infants born weighing 2,500 grams or less still account for two-thirds of neonatal deaths; ~ 9 those 1,500 grams or less account for half of neonatal deaths.4 ~ As mortality among normal birthweight infants decreases, this attr ibutable r isk is likely to increase. Thus, in industr Waltzed populations, the proportion of very low birthweight infants is a ma jor predictor of neonatal mortality.4 2 Even controlling for other factors known to affect the risk of neonatal mortality, low birthweight remains the major determinant of neonatal deaths 3 Postneonatal Mortality The relationship between postneonatal mortality and birthweight is not as sharp as that for neonatal mortality; however, low birthweight infants are 5 times more likely than normal birthweight infants to die later in the first year and account for 20 percent of all postneonatal deaths.~9 44 For very low birthweight infants, the relative risk of postneonatal death is 20 times that of normal birthweight infants, and these infants account for between 25 and 30 percent of postneonatal deaths.45 AS suggested by previous reports,23 25 the effect of bi rthweight on postneonatal mortality is modified by socioeconomic factor s. 4 3 Effect of Gestational Age and Other Risk Factors Within birthweight groups, the r isk of mortality is not uniform and var yes with gestational age. For a given birthweight the longer the duration of gestation up to 42 weeks, the lower the mortality.20 2 Similarly, for a given gestational age, again up to 42 weeks, the heavier infants have lower mortality rates.2 o 2 ~ In general, small for gestatzonal age (SGA) infants have lower neonatal and postneonatal mortality rates than appropr late for gestational age (AGA) infants of comparable birthweights. ~ o 4 6 The except ion is the full-term infant weighing 2,500 grams or lesser ° which has a higher mortality rate than term infants of normal ir thwe ight . The relative proportion of AGA and SGA infants among low birth- weight infants var. ies with different low birthweight rates . For populations in which the proportion of low birthweight infants exceeds 10 percent, SGA infants represent the majority of low birthweight infants.4 7 4 ~ At lower rates, of 5 to 7 percent, premature AGA infants are in the major ity. 4 7 4 8 The relative contr libations of AGA and SGA infants to neonatal mortality in the United States are not well established. Despite the difference in mortality rates between SGA and AGA infants at a given birthweight, the shift towards a higher proportion of AGA infants is unlikely to have much effect on the estimate of the proportion of per inatal deaths accounted for by low birthweight infants. When the relative effects of birthweight and gestational age on mortality have

30 been examined, birthweight has been the dominant factor .2 0 4 9 AS noted below, however, the shift may have implications for morbidity among surviving infants. Besides gestational age, other factors are associated with an increased risk of neonatal mortality. As noted earlier, race Is one such factor; others include maternal age at the extremes of the childbearing age range, low maternal educational attainment, and a history of prior adverse obstetrical outcomes such as fetal death.* These risk factors also are associated with high rates of low birthweight. Controlling for birthweight distribution sharply reduces or eliminates the differentials in neonatal mortality associated with several of these factors, namely, nonwhite race (especially black and American Indian), adolescent motherhood, and low maternal educational attainment.) 9 s ° This finding indicates that the proportion of low birthweight infants ~ argely accounts for the adverse neonatal mortality experiences of these subgroups. Differences in birthweight do not eliminate the increased risk of neonatal death associated with advanced maternal age and prior history of fetal loss.~9 These factors are associated with a combination of increased risk of low birthweight and increased obstetrical vulnerability. The situation is different for postneonatal mortality. Even after controlling for birthweight, postneonatal mortality rates remain higher for nonwE ite infants, infants of adolescent mothers, and infants of mothers of low educational attainment.~9 5 ° Thus, factors indicative of socioeconomic disadvantage are linked to increased infant mortality through both higher low birthweight rates and an increased risk of postneonatal death, regardless of birthweight. Current Decline In Neonatal Mortality After a period of relative stagnation in the 1960s, the infant mortality rate began its current rapid decline. In 1980, the infant mortality rate was 13.1 per 1,000 live births, a 47 percent decrease from the rate in 1965 .3 6 In contrast to the first half of the century, this recent change is primarily the result of a decrease in neonatal mortality. The accumulating evidence indicates that a major factor in this rapid decline has been the increased survival of low birthweight infants, in part as a result of more intensive, hospital-based management and of improvements in perinatal care, particularly for h~gh-risk pregnancies. Several different factors support this . conclusion: *In Chapters 2 and 3, these risk factors are discussed in more detail and an effort is made to isolate their independent effects.

31 · The decrease in neonatal mortality has occurred in the context of only modest decreases in the proportion of low birthweight infants. s ~ ~ s 3 · There has been a progressive decline in neonatal mortality among very low birthweight infants who receive intensive care. 12 · Decreases in neonatal mortality for geographically def ined areas have followed the introduction of per inatal intensive care unitS.s`-s6 · Low birthweight infants born in hospitals with intensive care facilities have a higher survival rate than infants born in hospitals without such units,s 7- 5 9 even after controlling for other risk factors known to affect survival.59 This enhanced survival rate persists even in comparisons involving infants transported to regional perinatal care centers shortly after birth.60 6 ~ · Decreases in neonatal mortality in geographically defined regions have been shown to accompany an increase in the proportion of low birthweight and very low birthweight births occurring in tertiary centers. 4 ~ Thus, the current decline In neonatal mortality can be attributed largely to increased survival of high-risk infants. I n many areas of the country, birthweight-specif~c mortality rates are now similar for high- and low-r~sk groups. This means that efforts to sustain the decline in neonatal mortality will have to focus on the prevention of low bir~chwe'ght in infants. Low Birthweight and Morbid ~ ty The contr ibution of low birthweight to morbidity in childhood is less well established than its contr ibution to infant mortality. In part, this results frown the relative lack of population-based morbidity data involving sufficient numbers of low birthweight infants. In addition, the types of morbidity that occur in low birthweight survivors, especially those at very low birthweight are still being identified. Finally, perinatal events are only one determinant of child health, and disentangling the effect of low birthweight from other factors and from the interactions among these factors has proved cliff icult. Still, the existing literature indicates that low birthweight infants appear to be at increased risk of a number of health problems and that this increased risk has implications for health services, and possibly for educational services and family function as well. Several health problems are discussed below; additional morbidity data are in Chapter 10. Neurodevelopmental Handicaps The prevalence of neurodevelopmental handicaps has been a primary focus in the follow-up of low bir thwe ight infants because the increased r isk of cerebral palsy, seizure disorders, and other neurodevelopmental

32 problems in these infants was documented in the 1950S.2 ~ - 3 ° At that time, the r Ask of neurodevelopmental problems for all low bir thweight infants was 3 times that of normal birthweight infants, and that for very low birthweight infants was 10 times that of normal birthweight infants.30 Much of the recent literature on neonatal birthweight has focused on the very low birthweight group. 3 6 2 - 6 ~ Recent reviewers t~ ~ 2 of this literature have concluded that the prevalence of neurodevelop- mental handicaps among very low birthweight survivors appears to be decreasing, although variations in data suggest cautious interpretation. Despite the evidence of a decrease, low birthweight infants remain 3 times as likely as normal birthweight infants to experience adverse necrologic sequelae, 6 s and the risk increases with decreasing birth- weight, so that 8 to 19 percent of very low birthweight infants may be severely affected.~ 3 6 6 6 7 Variations in outcome among very low birthweight survivors may be related to several factors. One that has received significant attention is cerebral intraventricular hemorrhage, probably caused by asphyxia. Although very low birthweight infants without ~ntraven- tricular hemorrhage remain at increased risk of adverse neurodevelop- mental outcomes as compared with a normal population, those with large hemorrhages (Grades 3 and 4 ~ are at substantially her eased risk of sever e handicap. 6 6 The risk of other developmental problems, especially those related to success in school, is less well established. It does appear, however, that low birthweight may be a significant predictor of school failure, 6 7 and this may be par ticularly character istic of those who are small for gestational age. ~ 4 6 ~ Even in the Sod groups, however, the proportion of handicapped may be dependent on the presence of birth asphyxia, rather than on birthweight per se.69 The risk of developmental delay is not independent of factors that act to increase the risk of low birthweight. Thus, the low birthweight infants of disadvantaged mothers are more likely to experience school failure,68 or to have lower intelligence quotients (IQs) , than infants of similar birthweight in more advantaged families.3 ° 7 0 The Risk of Congenital Anomalies Although ~ ess intensively studied, the increased relative r isk of congenital anomalies among low birthweight survivors is well documented. As compared with normal birthweight infants, low birthweight infants are twice as likely to have a nontrivial anomaly, and very low birthweight infants are 3 times as likely to have one.7 ~ Among the low birthweight infants, the risk of an anomaly is h igher for those who are small for gestational age than for those whose birthweight is more consistent with the duration of gestation. ~ 0 4 6 Congenital anomalies and neurodevelopmental handicaps are not mutually exclusive occurrences. The percentage of infants affected with one or both ranges from 19 percent of normal birthweight infants to 42 percent of very low birthweight infants (anomalies include the

33 presence of extra digits and strabismus, as well as more ser ious problems); those severely affected range from 2 percent of normal birthweight infants to 14 percent of very low birthweight infants. ~ 9 Respiratory Tract Conditions Low birthweight also is a r isk factor for the development of lower respiratory tract conditions . 7 2 Abnormal chest x-rays and pulmonary function and repeated lower respiratory tract infections often have been reported in low birthweight infants who had hyal~ne membrane disease or respiratory distress syndrome as newborns.7 3 - 7 ~ They also may occur in low birthweight infants who were asymptomatic in the neonatal per lad . 7 7 The persistence of abnormal cardiopulmonary function into early childhood is particularly character istic of those infants who required prolonged ventilatory support.79 8° Overall, 8 percent of very low birthweight infants have evidence of chronic pulmonary disease at 40 weeks of age (corrected for duration of gestation), but this proportion decreases to 3 percent by 20 months of age. ~ ~ The implications of these abnormalities for acute respiratory illness among surviving infants, especially illnesses that do not require hospitalization, have been only partially delineated. Complications of Neonatal Care Intensive care technology required for the survival of these infants is not without hazard, and may result in complications. The most well known is that seen with oxygen administration to immature infants, who may develop retrolental fibroplasia.~ 2 ~ 3 Other diagnostic and therapeutic techniques also have been shown to be hazardous." Today's special care units expose infants to many substances, machines, and environmental cond'~ions.8 4 - ~ 6 The potential side effects are still being defined. Nonspecific Morbidity Early studies suggested that low birthweight infants might be at greater risk of illness in general.8 7 Relatively few investigators have examined this issue, however, and their findings have varied. ~9 Recent data suggest that very low birthweight infants may be at increased r isk of relatively ser ious or protracted illness. At one year, about one-third of these infants have had an illness requir ing hospitalization and/or requiring prolonged care, as compared with 20 percent of all low birthweight infants and 17 percent of normal birthweight infants.~9 This may vary with age, because the proportion of very low birthweight infants with selected chronic conditions var. ies from 23 percent at 40 weeks of age (corrected for duration of gestation) to 3 percent at 20 months.8 ~ The susceptibility of high-risk survivors to acute or less ser ious illness remains to be established.

34 In jury The r isk of accidental in jury for low birthweight infants remains relatively unexplored. Up to 1 year of age, little difference In the risk of injury by birthweight occurs.8 9 Few studies have examined this association in older children. The relatively extensive literature identifying low birthweight as a risk factor for intentional injury (abuse) has been reviewed recently; the conclusion was that the evidence for such an association is not strong. 9 ° Use of Health Services Morbidity among low birthweight infants has significant implications for health services. Most of the interest in medical care use by low birthweight infants has focused on the intensive care services required to increase the survival of very low birthweight infants. The length of hospital stay in the neonatal period for infants who survive to the first year of life averages 3.5 days for normal birthweight infants, but is much longer for smaller infants: 7 days for those between 2 ,001 and 2, 50 0 grams at bir th; 24 days for those between 1, SO ~ grams and 2 ,000 grams; 57 days for those less than 1,500 grams; 4 5 and 89 days for those less than 1,000 grams.9 ~ The length of stay for nonsurviving infants tends to be much less, although not proportionally less e~ensive.9t 92 Wide variations both in length of stay and direct medical costs per day occur within birthweight groups, depending on the need for ventilation, the presence of congenital anomalies, the need for surgery, and other factors. 9 3 The cost-effectiveness of neonatal intensive care has been ques- tioned. A recent review has concluded that it is generally cost- effective. ~ ~ Some individuals have expressed doubts, however, as to whether this conclusion will hold for the very smallest infants (1,000 grams or less). The results depend on the ad justments made for futur e costs incurred by handicapped survivors. 9 ~ In addition to under going prolonged hospitalization at birth, a substantial proportion of very low birthweight infants are rehospital- ized during the first year.9s 96 Up to 40 percent of these infants will have almost two hospitalizations, for an average of 16 days. This compares with 19 percent of all low birthweight infants for an average of 12 e 5 days, and 8. 7 percent of normal birthweight infants for an average of 8 days.95 A major determinant of rehospitalization for all birthweight groups is the presence of a chronic condition, congenital anomaly, or poor developmental outcome.95 96 After In fancy, hospital use diminishes sharply. 9 6 The average number of physician visits also is higher for low birthweight infants than for normal birthweight infants, but the relationship to birthweight is not as sharp as that for hospitalization. In one study, average visits in the first year ranged from 14 to 16 for those less than 1, 500 grams at birth, to 10 for normal birthweight infants. As with hospitalization, a major determinant of physician utilization is the presence of a congenital anomaly and/or developmental delay. 9 ~

35 It is perhaps worth emphasizing that, on a population basis, the conditions for which medical services are used by low birthweight infants, even very low birthweight infants, are similar to those occasioning the use of services by normal birthweight infants.95 9 7 These include congenital anomalies; respiratory infections such as pneumonia, bronchitis, and ot~tis media; and gastrointestinal problems. The increased use of services by low bir thweight infants reflects the increased prevalence of these conditions. The etiologic basis for this increased morbidity and increased use of services has been only partially def ined. Contributing factors may include biologic vulner ab ~ 1 Sty due to immaturity, residual effects from the therapeutic maneuvers required to support the infants, socioeconomic disadvantages characteristic of many low birthwe~ght infants, and increased surveillance by health care providers and parents. Family Function Finally, the birth of a h~gh-risk infant may have major implications for family function. Early attempts to manage low birthweight infants produced an incidental observation of an apparent decrease in attachment between the mother and the surviving low birthweight infant.98 Much recent work suggests that the bonds between mothers and critically ill infants may be disrupted so extensively that inappropriate parenting behaviors emerge.99 ~°° In the extreme, this is seen as overprotectiveness ~ ° ~ ~ o 2 or physical abuse,~° 3 ~ O ~ although the data on the latter may be questioned on methodological grounds.90 More subtle indications of this disruption include altered perceptions and attitudes toward the low birthweight infant, which could have adverse consequences for the chides future development. ~ o s ~ o 6 The etiology of this maladaptive parenting remains unclear. Early investigators linked these changes to separation of the mother and infant required for intensive management.99 ~°° Other work has suggested that the physical appearance of the ch~ld,~07 parental anxiety generated by the critical status of the infant at b~rth,~°5 continued illness after discharge from the nursery,~° 4 and tempera- mental differences in the infantile also may contribute to altered parent-child interactions. Most likely, many of these factors operate together. 06 Little information is available on other effects of h~gh-risk infants on family function. Numerous studies of children with different chronic or catastrophic illnesses suggest, however, that the usual patterns of family function may be disrupted substantially. Serious and/or chronic illness in children has been associated with mar ital instability, ~ ° 9 altered parental employment opportunities and family income,~° decreased social contacts and vacations as a result of the burden of care for the chit d and the lack of alternate care-givers, ~ ~ problems in other children in the family, ~ 2 and increased workload for the mothers.~3

36 Long-term assessments of family function fold owing the birth of a low birthweight infant are just beginning to be reported. At least one study supports concerns in this regard. In this study,70 high levels of behavior problems were found among preschoolers who were born at very low birthweight, and these problems were associated with decreased performance on standardized IQ tests. Financial Stress The degree of financial stress experienced by the families of high-risk infants may be another relevant factor. In the neonatal period, a substantial proportion of direct medical charges may be borne by the parents, up to 5 percent of the total for those with insurance and up to a third for those without insurance. g 2 The amount of posed' scharge care, both inpatient and ambulatory, absorbed by the family is not known, but likely to be high. In general, 15 to 20 percent of the costs of hospital care and 70 percent of the costs of outpatient care and medical suppliers 4 - ~ ~ 7 for children are paid out of pocket by the family. It has been shown that insurance coverage affects the use of inpatient services regardless of health problems for low birthweight infants95 and that family income, as well as insurance, affects the use of ambulatory services.9 7 Almost no information is available on indirect costs, such as alterations In opportunities for maternal participation in the work force and time lost from work to obtain medical care, although the costs of visiting the child in the neonatal period have been estimated recently. Whatever the expenditures' stress levels in some of these families are likely to be high, because these are young parents just beginning their working lives. Overall Contribution of Low Birthweight to Morbidity Despite the many conditions to which low birthweight infants may be vulnerable, the overall contribution (attributable risk) of birthweight- related conditions to morbidity is quite small. Low birthweight infants are only 1.6 times more likely to have a congenital anomaly, with or without developmental delay, than a normal birthweight infant; they account for 6 percent of infants with these conditions--about their representation in the population.~9 For very low birthweight infants, the relative risk is only 3.3 times that of normal birthweight infants.~9 For more severe conditions, the relative and attributable risks are smaller.~9 In particular, the proportion of very low birthweight survivors with serious illnesses diminishes rapidly after the first year,8i so the effect of low birthweight infants on morbidity ~ ater in the preschool period is likely to be small. The contr ibution of low birthweight i nfants to the population of children with school and behavioral problems cannot be estimated, but again the effect is unlikely to be as overwhelming as that of low birthweight on mortality.

37 These conclusions may seem inconsistent with data on increased risk of morbidity, but the risk of morbidity from low birthweight is much smaller than the risk of mortality. In addition, because of their higher mortality rates, low birthweight infants constitute a smaller proportion of all infants who survive their first year of life than of live births. ThuS, the effect of low birthweight in infants on childhood morbidity is substantially less than its effect on mortality. This optimistic assessment must be tempered, however, by the realization that the full range of morbidity experienced by these infants is still being def i ned. Outcomes among the newest group of surviving babies, those weighing less than 1, 000 grams, are generally unknown. Although they represent a relatively small proportion of surviving children, these high-risk infants often have health problems that require special services. This suggests that more research is required to evaluate the morbidity experienced by these infants and to determine the appropriate structure and target population for effective management strategies. Decreasing Mortality: The Effect on Morbidity Reviews of the outcomes among survivors of intensive care have documented decreases in the proportion of infants with adverse outcomes over time. 12 Interpretation of these reviews must be cautious, however, because the proportion of children with adverse outcomes has varied significantly among the studies and because selection factors affecting referral to intensive care units might alter the results. More recent data based on clinical series 6 ~ ~ ~ and population- based morbidity surveys ~ 9 indicate that the increased survival of low birthweight infants has not been associated with an increase in the number with handicaps. The proportion with severe congenital anomalies and/or developmental delay has remained the same6 4 ~ ~ 9 whereas the proportion with less severe morbidity associated with antenatal and intrapartum events has declined.~9 As noted earlier, however, concerns remain about the effect of increased survival of the very smallest infants, those less than 1,000 grams.9 6 Summary Low b~rthweight is a major determinant of infant mortality. Most infant deaths occur in the first month of life, or neonatal period. The majority of these deaths are a consequence of inadequate fetal growth as indicated by low birthweight (birthweight of 2 , 500 grams or less). Inadequate fetal growth may result from shortened duration of gestation or prematur ity (duration of pregnancy less than 37 weeks from the last menstrual per iod), poor weight gain for a given duration of pregnancy ~ ~ntrauter fine growth retardation), or a combination of the two. The r Ask of mortality increases with decreasing birthweight so the smallest infants (very low birthweight or infants born weighing 1,500 grams or less) are at greatest r isk .

38 The proportion of low birthweight infants is not only a major determinant of the overall neonatal mortality rate for a given population, but also is an important factor in the differences in neonatal mortality rates among different subgroups in the Papua ation. Thus, the higher neonatal mortality rates seen for nonwhite mothers, teenage mothers, and mothers of low educational attainment are explained by higher proportions of low birthweight infants among these groups. In addition to increasing the risk of mortality, low birthweight increases the risk of morbidity. Although low birthweight is not a major determinant of the total burden of morbidity among infants and children, the relative risk of morbidity among low birthweight infants is high. The association of neurodevelopmental handicaps and congenital anomalies with low birthweight has been well established; low birthweight infants also may be susceptible to a wide range of other conditions, such as lower respiratory tract infections, learning disorders, behavior problems, and complications of neonatal intensive care interventions. Moreover, the birth of a low birthweight infant and its subsequent problems may place substantial emotional and f inancial stress on a young family; ache consequences of this stress ar e still being studied. Although the neonatal mortality rate in the United States has dropped significantly over the past 15 years, this change has not been associated with a comparable decrease in the incidence of low-we~ght births . Instead, the decline has resulted from the increased survival of low birthweight infants, due largely to more specialized, hospital-based management through neonatal intensive care. The proportion of infants born at low birthweight has changed only modestly since the late 1960s, and little change has been seen in the proportion of infants born at very low birthweight. The current statistics suggest that further reductions in neonatal mortality and decreases in the differentials between high- and low-mortality subgroups will require the prevention of low birthweight in infants. References and Notes 1. Silverman WA: Retrolental Fibroplas~a: A Modern Parable. New 3. 4. York: Grune and Stratton, 1980. 2. Cone TE Jr: De pondere infantum recens natorum: The history of weighing the newborn infant. Pediatrics 28:490-498, 1961. Rooth G: Low birthweight revised. Lancet 1:639-641, 1980. World Health Organization: Manual of the International Statistical Classification of Diseases, Injuries and Causes of Death, Sixth Revision, Adopted 1948. Geneva: World Health Organization, 1948. 5. World Health Organization: Report on the Second Session of the Exper t Committee on Health Statistics . Technical Repor t Ser ies, No. 25. Geneva: World Health Organization, 1950. Be Shapiro S: Influence of birthweight, sex and plurality on neonatal loss in the United States. Am. J. Public Health 44: 1142-1153, 1954 .

39 7. McKeown T and Gibson JR: Observations on all births (23,970) in Birmingham, 1947. II. Birthweight. Br. J. Soc. Med. 5:98-112, 1951. 8. Taback M: Birthweight and length of gestation with relation to prematurity. JAMA 146:897-901, 1951. 9. World Health Organization Expert Committee on Maternal and Child Health: Public Health Aspects of Low Birthweight. Third Report of the Expert Committee on Maternal and Child Health. Technical Report Series, No. 217. Geneva: World Health Organization, 1961. 10. Van den Berg BJ and Yerushalmy J: The relationship of intrauterine growth of infants of low birthweight to mortality, morbidity, and congenital anomalies. J. Pediatr . 69: 531-545, 1966. 11. Office of Technology Assessment, U.S. Congress: The Implications of Cost-Effectiveness Analysis of Medical Technology. Background Paper No. 2: Case studies of medical technologies. Case Study No. 10: The costs and effectiveness of neonatal intensive care. Prepared by P Budetti, MA McManus, N Bar r and, and LA Heinene GPO Stock No. 052-003-00845-9. Washington, D.C.: U.S. Government Printing Office, 1981. 12. Stewart AL, Reynolds ED, and Lipecomb AP: Outcomes for infants of very low birthweight: Survey of world literature. Lance t I: 1038-1040, 1981. 13. Fitzhardinge PM: Follow-up studies of the low Birthweight infant. Clin. Per inatal. 3: 503-516, 1976 . 14. Fitzhardinge PM and Steven EM: The small-for-date infant. II. Neurologic and intellectual sequelae. Pediatrics 50: 50-57, 1972. 15. Blalock NM: Social Statistics. New York: McGraw-Hill, 1960. 16. Wilcox Ad and Russell IT: Birthweight distribution and perinatal mortality. I. On the frequency distribution of birthweight. Int. J. Epidemiol. 12: 314-318, 1983 . 17. Wilcox AJ and Russell IT: Perinatal mortality: Standardizing for birthweight is biased. Am. J. Epidemiol. 118: 857-864, 1983 . 18. Weaver JL: Policy responses to complex issues: The case of black infant mortality. J. Health Politics Policy Law 1:433-443, 1977. 19. Shapiro S. McCormick He, Starfield BE, Krischer JP, and Bross D: Relevance of correlates of infant deaths for significant morbidity at 1 year of age. Am. J. Obstet. Gynecol. 136: 363-373, 1980. 20. Williams RL, Creasy RK, Cunningham Go, Hawes WE, Norris FD, and Tashiro M: Fetal growth and perinatal viability in California. Obstet. Gynecol. 59: 624-632, 1982. 21. Roops BL, Morgan LJ, and Battaglia FC: Neonatal mortality risk in relation to birth weight and gestational age: Update. J. Pedlatr . 101: 969-977, 1982 . 22. Morris JN and Heady JA: Social and biological factors in infant mortality. Lancet I: 343-349, 1955. Pharoah POD and Morris JN: Rev. 1:170-183, 1979. 24. Puffer RR and Serrano CV: Patterns of Mortality in Childhood. Washington, D.C.: Pan American Health Organization, 1973. Post-neonatal mortality. Epidemiol

40 25 . Shapiro S. Schlesinger ER, and Nesbitt REL : Infant, Per inatal, Maternal and Childhood Mortality in the United States. Cambr idge , Mass .: Harvard University Press , 1968 . 26. National Center for Health Statistics: Factors Associated with Low Birthweight: United States, 1976. Prepared by S Taffel. Vital and Health Statistics, Series 21, No. 37. DREW No. {PHS) 80-1915. Public Health Service. Washington, D.C.: U.S. Goverrment Pr inting Of f ice, Apr. il 1980 . 27. Lilienfeld AM and Parkhurst E: A study of the association of factors of pregnancy and parturition with the development of cerebral palsy: A preliminary report. Am. J. Hyg. 53 :262-282, 1951. 28. Lilienfeld AM and Pasamanick E: Association of maternal and fetal factors with the development of epilepsy: Abnormalities in the prenatal and per inatal per iods. JAMA 155: 719-724 7 1954 . 29. Niswander RR and Gordon M: The Women and Their Pregnancies: The Collaborative Per inatal Study of the National Institute of Neurologic Diseases and Stroke. Philadelphia: W.B. Saunders, 1972. 30. Hardy JB, Dr age JS, and Jackson EC: The First Year of Life: The Collaborative Per inatal Study of the National Insti tute of Neurological and Communicative Disorders and Stroke. Baltimore: Johns Hopkins University Press, 1979. 31. Abramowicz M and Rass EH: Pa~hogenesis and prognosis of prematur ity. N. Engl. J. Med. 275: 878-885, 938-943, 1001-1007, 1053-1059, 1966. 32. Aubrey RB and Pennington JC: Identification and evaluation of higher isk pregnancy: The per inatal concept. Clin. Obstet . Gynecol. 16:3-27, 1973. 33. Hobel CJ, Youkeles L, and Forsythe A: Prenatal and intrapartum higher isk screening . II . Risk factors reassessed. Am. J. Obstet. Gynecol. 135: 1051-1056, 1978. 34. Davis R and Schoen C: Health and the War on Poverty: A Ten Year Appraisal. Washington, D.C.: The Brookings Institute, 1978 . 35. Select Panel for the Promotion of Child Health: Analysis and Recommendations for Selected Federal Programs. Better Health for Our Children: A National Strategy. Vol. II. DHHS No. (PHS) 79-55071. Public Health Service. Washington, D.C.: U.S. Government Printing Office, 1981. National Center for Heal th Statistics: Health, United States, 1982. DHES No. (PHS) 83-1232. Public Health Service. Washington, D.C.: U.S. Government Printing Office, December 1982. 37. Susser M, Marolla FA, and Fleiss J: Birthweight, fetal age and per inatal mortality. Ala. J. Epidemiol. 96 :197-204, 1972. 38. Rooth G: Better perinatal health: Sweden. Lancet II:1170-1172, 1979. 3 9. Lumley J: Better per inatal health: Australia. Lancet I: 79-81, 1980. 4 0 . Backet EM, Davies AM, and Petros-Barvaz fan A: The Risk Approach in Health Care: With Special Reference to Maternal and Child Health, Including Family Planning. Publ, c Health Papers, No. 76 . Geneva: World Health Organization, 1984 .

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42 71. 73. Williams RL and Hawes WE: Cesarean section, fetal monitor ing and per inatal mortality In California. Am. J . Public Health 69: 864-870, 1979 . Hein HA and Brown CJ: Neonatal mortality review: A basis for improving care. Pediatr ics 68: 504-509, 1981. 59. Paneth N. Kiely JL, Wallenstein S. Marcus M, Pakter J. and Susser M: Newborn intensive care and neonatal mortality in low-birthweight infants. N. Engl. J. Med. 307 :149-155, 1982. 60. Haines TR, Isaman 3, and Giles HR: Improved neonatal survival through maternal transport. Obstet. Gynecol. 52: 294-300, 1978 . 61. Modanlou ED, Dorchester W. Freeman RK, and Rommal C: Perinatal transport to a regional perinatal center in a metropolitan area: Maternal versus neonatal transport. Am. J. Obstet. Gynecol. 138:1157-1164, 1980. Sabel RG, Olegard R. and Victoria L: Remaining sequelae with modern per inatal care. Pediatr ics 57: 652-658, 1976 . 63. Stewart A, Turcaro D, Rawl~ngs S. Hart S. and Gregory S: Outcome for infants at high r isk of ma jor handicap. In Ma jor Mental Handicap: Methods and Costs of Prevention. CIBA Foundation Symposium 59, pp. 151-171. Amsterdam: Elsevier-Excerpta Medica, 1978. Hack M, Fanaroff AA, and Merkatz IR: The low-birthweight infant: Evolution of a changing outlook. N. Engl. J. Med. 301:1162-1165, 1979 . 65. McCormick MC, Wessel KW, Krischer JP, Welcher DW, and Handy JB: Preliminary analysis of developmental observations In a survey of morbidity in infants. Early Hum. Devel. 5:377-393, 1981. 66 . Papile L, Munsick-Bruno G. and Schaefer A: Relationship of cerebral intraventr~cular hemorrhage and early necrologic handicaps. J. Pediatr. 103:273-277, 1983. 67. Ramey CT, Stedman DJ, Borders-Patterson A, and Mengel W: Predicting school-failure from information available at birth. Am. J. Ment. Def ic. 82: 525-534, 1978. 68. Harvey D, Prince J. Bunton J. Parkinson C, and Campbell S: Abilities of children who were small-for-gestational-age babies. Pediatrics 69:296-300, 1982. 69. Westwood M, Kramer MS, Munz 0, Lovett JM, and Watters GV: Growth and development of full-term nonasphyxiated small-for- gestational-age newborns: Follow-up through adolescence. Pediatrics 71:376-382, 1983. 70. Escalona SK: Babies at double hazard: Early development of infants at biologic and social r isk . Pedants ics 70: 670-676, 1982 . Christianson RE, Van den Berg BJ, Milkovich L, and Oechsli FW: Incidence of congenital anomalies among white and black live births with long-term follow-up. Am. J . Public Health 71:1333-1341, 1981. 72. McCall MG and Acheson HG: Respiratory disease in infancy. J. Chronic Dis. 21:349-359, 1968. Outerbr~dge EW, Nogrady MB, Beaudry PH, and Stern L: Idiopathic respiratory distress syndrome. Am. J. Dis. Child. 123:99-104, 1972.

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Despite recent declines in infant mortality, the rates of low birthweight deliveries in the United States continue to be high. Part I of this volume defines the significance of the problems, presents current data on risk factors and etiology, and reviews recent state and national trends in the incidence of low birthweight among various groups. Part II describes the preventive approaches found most desirable and considers their costs. Research needs are discussed throughout the volume.

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