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Low birth weight in the United States1–3

Robert L Goldenberg and Jennifer F Culhane

ABSTRACT weight (LBW) is an important cause of perinatal mortality and


Pregnancy outcomes in the United States and other developed coun- both short- and long-term infant and childhood morbidity. LBW
tries are considerably better than those in many developing coun- infants die at rates of up to 40 times those of infants of normal
tries. However, adverse pregnancy outcomes are generally more weight, and LBW infants are many times more likely to end up
common in the United States than in other developed countries. with long-term handicapping conditions (Figure 1). This article
Low-birth-weight infants, born after a preterm birth or secondary to will explore issues related to the causes, outcomes, and interven-
intrauterine growth restriction, account for much of the increased tions used to prevent LBW.
morbidity, mortality, and cost. Wide disparities exist in both preterm
birth and growth restriction among different population groups. Poor
and black women, for example, have twice the preterm birth rate and

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DEFINITIONS OF LOW BIRTH WEIGHT
higher rates of growth restriction than do most other women. Low
birth weight in general is thought to place the infant at greater risk of LBW is not a homogeneous pregnancy outcome, but instead,
later adult chronic medical conditions, such as diabetes, hyperten- conceptually, is composed of infants who are either born too
sion, and heart disease. Of interest, maternal thinness is a strong early, ie, preterm birth, or too small, ie, with fetal growth restric-
predictor of both preterm birth and fetal growth restriction. How- tion. According to the World Health Organization, a LBW infant
ever, in the United States, several nutritional interventions, including is one born weighing 쏝2500 g (5). Preterm infants are those born
high-protein diets, caloric supplementation, calcium and iron sup- at 쏝37 wk from the first day of the last menstrual period, regard-
plementation, and various other vitamin and mineral supplementa- less of birth weight, whereas growth-restricted infants are those
tions, have not generally reduced preterm birth or growth restriction. born weighing less than the 10th percentile of birth weight–for–
Bacterial intrauterine infections play an important role in the etiol- gestational age, regardless of whether that weight is 쏝2500 g
ogy of the earliest preterm births, but, at least to date, antibiotic Thus, it is possible for both preterm and growth-restricted infants
treatment either before labor for risk factors such as bacterial vagi- to weigh 쏜2500 g.
nosis or during preterm labor have not consistently reduced the To define growth restriction, one needs a set of birth weight–
preterm birth rate. Most interventions have failed to reduce preterm for– gestational age standards with the 10th percentile birth
birth or growth restriction. The substantial improvement in newborn weights defined (6). Many such standards have been published,
survival in the United States over the past several decades is mostly and the 10th percentile birth weights vary substantially among
due to better access to improved neonatal care for low-birth-weight them. There are many issues related to the choice of which set of
infants. Am J Clin Nutr 2007;85(suppl):584S–90S. standards to use (6). Although these will not be reviewed in detail
here, it is clear that if one bases the standard on birth populations
KEY WORDS Low birth weight, preterm birth, fetal growth such as those found in Scandinavia, the 10th percentile cutoff for
restriction, cerebral palsy, neonatal mortality, stillbirth fetal growth restriction will be substantially higher than if the
standard is based on a predominantly black birth population in
the United States or a population of births from the Indian sub-
INTRODUCTION continent. Within the United States, whether the birth population
Pregnancy outcomes in the United States and other developed used to create the standard is a population at sea level or a
countries are considerably better than those seen in many devel- population living at high elevations such as Denver, CO, also
oping countries (1, 2). Stillbirth rates are in the range of 3–7 per makes a difference. In any case, the reasons to choose one birth
1000 births versus 욷30 in many developing countries. Neonatal population to use as a standard versus another have been dis-
mortality rates are 앒4 – 6 per 1000 newborns versus 욷40 per cussed in detail, and suffice it to say which standard to use is still
1000 newborns in developing countries, and maternal mortality a controversial topic.
rates are in the range of 5–10 per 100 000 pregnancies versus 1
rates as high as 500 –1000 per 100 000 pregnancies in some From Drexel University, Department of Obstetrics and Gynecology,
Philadelphia, PA.
developing countries. Nevertheless, despite these better out- 2
Presented at the conference “Maternal Nutrition and Optimal Infant
comes in developed countries, adverse pregnancy outcomes are Feeding Practices,” held in Houston, TX, February 23–24, 2006.
generally more common in the United States than in other de- 3
Reprints not available. Address correspondence to RL Goldenberg, De-
veloped countries and result in both excessive medical costs in partment of Obstetrics/Gynecology, Drexel University College of Medicine,
the perinatal period and increased long-term neurologic disabil- 245 North 15th Street, 17th Floor, Room 17113, Philadelphia, PA 19102.
ity (3, 4). In both developed and developing countries, low birth E-mail: rgoldenb@drexelmed.edu.

584S Am J Clin Nutr 2007;85(suppl):584S–90S. Printed in USA. © 2007 American Society for Nutrition
LOW BIRTH WEIGHT IN THE UNITED STATES 585S

FIGURE 3. Etiology of preterm birth.

FIGURE 1. Sequelae of preterm birth.


wk (8). Thus, somewhere between two-thirds and three-quarters
of all stillbirths are preterm and generally LBW. Both fetal
NEONATAL OUTCOMES ASSOCIATED WITH LOW
growth restriction and preterm birth are important risk factors for
BIRTH WEIGHT
stillbirth.
The important birth outcomes related to LBW include both
fetal and neonatal death, postneonatal death, short-term morbid-
ities such as respiratory distress syndrome and necrotizing en-
PRETERM BIRTH

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terocolitis, and long-term morbidities such as blindness, deaf-
ness, hydrocephaly, mental retardation, and cerebral palsy. The incidence of preterm birth in the United States is tradi-
However, whether an infant is preterm or growth restricted, if it tionally stated to be about 10%. In fact, over the past 25 y, the
has no short-term morbidity, is discharged from the hospital at preterm birth rate in the United States and in most other devel-
the usual time, and suffers no long-term morbidity or mortality, oped countries has risen (9, 10). In the United States, this increase
it matters little whether the infant was born growth restricted or has been from about 9.5% to 12.5% (Figure 2). Although most
preterm. Thus, many investigators use preterm birth and growth other developed countries have substantially lower preterm birth
restriction as a surrogate or intermediate outcome measure for rates than does the United States, many have experienced similar
serious morbidity or mortality. Said differently, the goals of rises in the preterm birth rate over the past several decades.
reducing growth retardation or preterm birth are important only Preterm birth is generally thought of as having 3 obstetric
as they reflect reductions in morbidity and mortality. It is possi- precursors (Figure 3). The first is an indicated preterm birth,
ble, and even likely, that in some circumstances, if handicap or usually for maternal or fetal indications. These births occur be-
death is avoided, delivering an infant early is not the worst of all cause the physician believes the fetus would do better in the
possible outcomes. nursery than in the uterus. Labor is either induced or the fetus is
delivered by elective cesarean delivery. Common reasons for
these decisions include fetal distress, which is usually deter-
STILLBIRTH AND LOW BIRTH WEIGHT mined by electronic fetal monitoring; severe growth restriction,
The relation between stillbirth and LBW is often not consid- which is usually determined by fetal ultrasound; maternal pre-
ered (7). However, it is important to understand that in the United eclampsia; and placental abruption. In most studies, about 25%
States, approximately one-half of all stillbirths occur at 쏝28 wk of all preterm births occur for maternal or fetal indications. The
gestational age, and another one-third occur between 28 and 36 rest of the preterm births are classified as spontaneous. These

FIGURE 2. Incidence of preterm birth in the United States, 1981–2002. Source: National Vital Statistics Report (10).
586S GOLDENBERG AND CULHANE

FIGURE 4. Temporal changes in all preterm births and those resulting from
FIGURE 5. Approximate prevalence of cerebral palsy per 1000 births by
ruptured membranes, medically indicated reasons, and spontaneous preterm
birth weight and gestational age.
birth, United States, 1989 –2000. Source: adapted from Ananth et al (11).

follow premature rupture of the membranes or spontaneous pre- same group of infants approaches 80%. Improvement in survival
term labor, regardless of whether the delivery ultimately is vag- over the past decades for infants between born weighing between

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inal or by cesarean delivery. In most studies, about 50% of all 1000 and 2500 g is equally impressive. With these improve-
preterm births follow spontaneous preterm labor and about 30% ments, mortality in infants born weighing 1000 to 2500 g is quite
follow premature rupture of the membranes. rare, and when one examines the distribution of neonatal mor-
Ananth et al (11) attempted to define the reasons for the in- tality by birth weight group, 앒60% of all neonatal mortality is
crease in preterm births over the past decade and a half. In an found in infants weighing 쏝1000 g. Thus, if we are to have a
analysis using US vital statistics data, they concluded that a large really large effect on neonatal mortality in the United States, our
part of the increase in preterm births in singletons is explained by major goal must be to reduce mortality in infants born weighing
an increase in indicated preterm births (Figure 4). Other authors 쏝1000 g.
have emphasized the considerable increase in preterm births There are several long-term outcomes associated with both
associated with multiple births that occur after the use of various preterm birth and fetal growth restriction. Among the best stud-
assisted reproductive techniques (12). At least one study in Can- ied are neurologic outcomes such as cerebral palsy, blindness,
ada suggested that a portion of the increase in spontaneous pre- deafness, and hydrocephaly. The earlier the gestational age and
term births was associated with an increase in chorioamnionitis the lower the birth weight, the greater the risk of all complications
(13). In any case, putting together all available data, it appears as and especially cerebral palsy (15). For example, as shown in
if indicated preterm births and multiple births secondary to as- Figure 5, that in infants born weighing 쏜2500 g at term, the risk
sisted reproductive technologies account for the vast majority of of cerebral palsy is 1 to 2 per 1000 births. On the other hand, for
the increase in preterm births noted above. infants born at the edge of survival (at about 23–24 wk and at
500 – 600 g), the prevalence of cerebral palsy is as high as 250 per
1000 births. In 1998, Lorenz et al (16) performed a meta-analysis
RACE, ETHNICITY, AND LOW BIRTH WEIGHT
of studies that presented survival and the prevalence of disability
For unknown reasons, belonging to various racial and ethnic in extremely LBW infants. As shown in Figure 6A, from 1975
groups is very strongly associated with both preterm birth and to 1995, survival among these extremely small infants increased
growth restriction. For example, in the United States, black substantially. On the other hand, the prevalence of disability
women are approximately twice as likely to have a preterm birth among the extremely small survivors remained virtually un-
and are 3 to 4 times as likely to have a very early preterm birth as changed over time, averaging about 25% (Figure 6B). Thus,
women are from most other racial or ethnic groups (14). East because the survivors increased and the prevalence of disability
Asian women typically have low rates of preterm birth, as do among the survivors stayed the same, the absolute number of
Hispanic women. Women from South Asia and especially the survivors with disability increased (Figure 6C). In an attempt to
Indian subcontinent have very high rates of fetal growth restric- show how this might play out for all births in the United States,
tion and low birth weight. Among all the various groups living in we constructed Table 1. It can be seen that from 1960 to 2000,
the United States, the very high preterm birth rate in black women 앒20 000 infants were born each year weighing 쏝1000 g. How-
stands out and to this date remains mostly unexplained. ever, survival increased from 앒1% in 1960 to 앒80% in 2000.
The number of survivors has increased accordingly. Since the
percentage of survivors with cerebral palsy or with any dis-
LOW-BIRTH-WEIGHT OUTCOMES ability has remained approximately the same, one can see that
One of the very large success stories in the United States and among the 20 000 infants born each year weighing 쏝1000 g,
other developed countries is the improved survival in very LBW the number of survivors with cerebral palsy and the number of
infants over the past 3 decades. For example, if one focuses on survivors with other disabilities has increased substantially
infants born weighing between 500 and 1000 g, in 1975, survival over the years. Thus, the major success related to preterm birth
for those infants was 앒15%. At the present time, survival for the is a reduction in mortality. There obviously has been no
LOW BIRTH WEIGHT IN THE UNITED STATES 587S
In relation to growth restriction, it appears that long-term dis-
ability is related to the degree of growth restriction (17). Those
infants born between the 5th and 10th percentiles, for example,
have little increase in long-term neurologic damage. On the other
hand, infants born below the 3rd and especially below the 1st
percentile are at considerably greater risk. The prevalence of
long-term handicap also depends on the gestational age at which
the growth restriction became established. For example, when
growth restriction is documented before 26 wk, the infants are
considerably more likely to have cerebral palsy or other neuro-
logic damage than are infants who grew appropriately the past 26
wk and then ceased growing normally. In any case, the risks of
cerebral palsy associated with growth restriction (쏝1%), espe-
cially if the infant is born close to term, are considerably less than
for preterm infants born weighing 500 –1000 g, for which overall
risk is 앒8%.

CHRONIC DISEASES ASSOCIATED WITH LOW BIRTH


WEIGHT
In recent years, there has been a great deal of interest in the

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relation of LBW and each of its components to the development
of long-term chronic medical conditions, such as hypertension,
diabetes, and heart disease. Termed the Barker Hypothesis, this
relation has been studied extensively, and although its existence
is controversial, it is supported by the results of several epide-
miologic studies (18). However, no interventions have been
shown to reduce the long-term chronic diseases potentially as-
sociated with LBW.

PREDICTING PRETERM BIRTH


In the United States, many studies have focused on the pre-
diction of preterm birth in the hope that being able to predict
preterm birth would lead to its prevention (19). Conceptually, the
predictors for preterm birth might be divided into 1) demographic
characteristics such as race and poverty, 2) adverse health be-
haviors such as smoking, 3) maternal physical characteristics
such as body size and especially low body mass index (BMI; in
kg/m2), 4) medical obstetric history such as having a prior pre-
term birth, 5) biophysical characteristics such as the length of the
cervix as determined either by physical examination or ultra-
sound, and 6) a large number of biological fluid markers. Among
the strongest predictors of preterm birth are black race, maternal
thinness as measured by a low BMI (쏝20), a history of a prior
preterm birth and especially an early preterm birth, a short cer-
vical length as measured by ultrasound, and a positive test result
for cervical or vaginal fluid fetal fibronectin (20, 21). Unfortu-
nately, knowledge of the presence of any of these characteristics
has not been helpful in reducing the incidence of preterm birth.
FIGURE 6. Changes in pregnancy outcomes over time in extremely small
infants. (The size of the circle represents the size of the cohort.) Source:
adapted from Lorenz et al (16). (A) Survival rate for extremely small infants INFECTION AND PRETERM BIRTH
(쏝800 g) in relation to year of birth. (B) Prevalence of disability among Over the past 20 y, it has become apparent that many of the
extremely small survivors (쏝800 g) in relation to year of birth. (C) Percent- early spontaneous preterm births are associated with and prob-
age of extremely small (쏝800 g) live births surviving with at least one
disability in relation to year of birth. ably caused by intrauterine bacterial infections (22–24). The
organisms are usually vaginal in origin and ascend into the uterus
either before or early in pregnancy. The organisms are often of
reduction in preterm birth, and there appears to be little or no low virulence and the infections tend to be chronic, persisting for
reduction in long-term handicap, at least among the smallest weeks or months before the preterm labor or membrane rupture
survivors. initiates a spontaneous preterm birth. Ureaplasma urealyticum
588S GOLDENBERG AND CULHANE

TABLE 1
Cerebral palsy (CP) in infants weighing 쏝1000 g at birth

Survivors Survivors with any


Year Births 쏝1000 g Survival Survivors with CP1 disability2

n % n n n
1960 20 000 1 200 16 32
1985 20 000 40 8000 640 1280
2000 20 000 80 16 000 1280 2560
1
Assuming an 8% incidence in survivors consistently over time.
2
Assuming a 16% incidence in survivors consistently over time.

and mycoplasma hominis are the 2 most common organisms, but suggests that the relation between BMI and preterm birth is
쏜30 different bacteria have been identified. Many of these or- mediated through cervical length, in that women who are over-
ganisms are components of a chronic vaginal infection called weight and obese tend to have longer cervices, which seem to
bacterial vaginosis, a common condition associated with a 2-fold protect against spontaneous preterm birth (19).
increase in preterm birth. About 85% of spontaneous preterm Several interesting observations have related various risk fac-
births of fetuses weighing 쏝1000 g are thought to be caused by tors to growth restriction mediated by maternal BMI. For exam-
an intrauterine infection, but few of the later preterm births are ple, higher BMIs appear to protect the fetus against the effect of
associated with this condition. Many attempts have been made to smoking on growth restriction (27). Similarly, higher BMIs pro-
reduce preterm birth by using antibiotics, either in the prenatal tect the fetus from the effect of maternal stress on growth restric-

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period or during early labor. Although the results of a few studies tion (28). In a randomized clinical trial, low doses of aspirin
have been positive, most have failed to show a reduction in increased birth weight and newborn abdominal circumference,
preterm birth, and no authoritative US agency recommends the but this relation occurred only in thinner women (29). Finally, in
use of antibiotics to achieve a reduction in preterm birth (24). another randomized clinical trial, zinc supplementation in-
creased birth weight substantially, but only in thinner women
(30). Thus, some evidence suggests that maternal thinness is a
NUTRITIONAL ISSUES
risk factor for spontaneous preterm birth and fetal growth restric-
Because this is a conference devoted to nutritional issues, it is tion. Furthermore, at least 2 treatments that might reduce fetal
appropriate to briefly explore the relation between maternal body growth restriction and preterm birth seem to work only in women
habitus and LBW. In recent years, it has become clear from many who are thin. High BMIs seem to protect against 2 risk factors for
studies that thin women have a higher risk of having both preterm growth restriction, maternal smoking, and maternal stress. An-
and growth-restricted infants than do average-sized women (25, other interesting observation relating maternal BMI to an adverse
26). In fact, the relation seems to be essentially linear in that the pregnancy outcome is that women with high BMIs are more
thinner the woman, the greater the risk of both preterm birth and likely to have infants with neural tube defects, and folate sup-
fetal growth restriction. Conversely, the heavier the woman, the plementation seems to work less well in preventing neural tube
lower the risk. However, the heavier the woman, the greater the defects in these women (31). Thus, the relation of maternal body
risk of a wide variety of pregnancy-related complications such as habitus, various risk factors, and various interventions to improv-
chronic hypertension, preeclampsia and eclampsia, and diabetes. ing outcomes should be explored further.
In Figure 7, which is derived from data from the National Insti-
tute of Child Health and Human Development Preterm Predic-
NUTRITIONAL INTERVENTIONS
tion Study, it can be seen that as maternal BMI increases, the rate
of spontaneous preterm birth decreases (26). Some evidence Because maternal thinness has been associated with preterm
birth and growth restriction, several studies have been made of
nutritional interventions to reduce adverse pregnancy outcomes.
First, it is clear that folic acid reduces the prevalence of certain
congenital anomalies (32). It is also clear that in certain devel-
oping countries where near-starvation diets are common, nutri-
tional supplementation improves several outcomes, including
reducing mortality as well as decreasing preterm birth and
growth restriction (33). However, in the United States, virtually
all nutritional interventions used to reduce low birth weight or its
components, preterm birth and growth restriction, have failed
(34, 35). In fact, protein supplementation appears to have a neg-
ative effect on pregnancy outcome. Nutritional counseling pro-
grams have had minimal effects, if any, on pregnancy outcomes,
and caloric supplementation programs including WIC (the Spe-
cial Supplemental Nutrition Program for Women, Infants, and
Children) have been associated with only small increases in birth
FIGURE 7. Spontaneous and indicated preterm birth (PTB) by maternal weight, but no other important improvements in outcome. Sup-
body mass index. Source: adapted from Hendler et al (26). plementation during pregnancy with various minerals such as
LOW BIRTH WEIGHT IN THE UNITED STATES 589S
iron, calcium or zinc, and various vitamin preparations have not better understanding and use of newborn respirators and oxygen
consistently reduced preterm birth or growth restriction. delivery (42).

SUMMARY
STRATEGIES USED TO REDUCE LOW BIRTH WEIGHT
In summary, the issue of LBW, and especially its preterm birth
Many other strategies have been used in an attempt to reduce component, has proven to be one of the most difficult pregnancy-
LBW (34). These include a general increase in prenatal care and related issues to address. Although survival has improved, the
many of its components. Home uterine contraction monitoring, proportion of births born before term continues to increase and
for example, has not generally led to any decrease in preterm the rate of disability among the preterm survivors has not de-
birth and often is associated with an increase in the use of various creased. Continued research aimed at reducing the preterm birth
interventions that by and large have not been effective (34, 36). rate and disability among survivors is crucial if we are to achieve
Programs aimed at reducing adverse health behaviors, such as the substantial improvements in pregnancy outcome in the United
use of drugs, alcohol, or tobacco, have by and large not had a States.
major effect on reducing preterm birth or growth restriction (34).
We should emphasize here, however, that tobacco use is more RLG performed the literature review, presented the data at the conference,
distinctly associated with growth restriction than with preterm and wrote the first draft of the paper. JFC helped to conceptualize the project,
birth (37), and it is likely that the recent decline in tobacco use reviewed the data before presentation, and edited both the presentation and
the paper. Neither of the authors had any financial interest or conflict of
during pregnancy is associated with an overall increase in birth
interest with the study.
weight. Many other interventions such as bed rest, use of anti-
biotics to treat infection, home uterine activity monitoring to

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