Research Agenda to Investigate Preterm Birth

The purpose of this report has been to assess the state of the science on the causes of pre-term birth address the health, social-emotional, and economic consequences of preterm birth for children born preterm and their families and establish a framework for action in addressing the range of priority issues, including a research and policy agenda for the future. The preceding chapters have provided an overview of the current knowledge on the measurement of maturity in infants the range of...

Abstract

In 2004, 12.5 percent of births in the United States were preterm that is, born at less than 37 completed weeks of gestation. This rate has increased steadily in the past decade. There are significant, persistent, and very troubling racial, ethnic, and socioeconomic disparities in the rates of preterm birth. The highest rates are for non-Hispanic African Americans, and the lowest are for Asians or Pacific Islanders. In 2003, the rate for African-American women was 17.8 percent, whereas the...

Air Pollution

A significant and relatively recent effort has been made to link environmental air pollution exposures with preterm birth. Recent reviews examined a subset of articles on this topic in detail and drew different conclusions (Maisonet et al., 2004 Sram et al., 2005). Sram et al. (2005) reported that the evidence was insufficient to derive conclusions about an association between air pollution exposure and preterm birth and that further studies were justified. In contrast, Maisonet et al. (2004)...

Alcohol

High levels of alcohol use during pregnancy have obvious adverse effects on fetal development (AAP, 1993 Spohr et al., 1993). There is consistent support of an adverse effect for heavier users of alcohol for example, women who have more than one drink per day, on average, have an increased risk of preterm birth (Albertsen et al., 2003 Kesmodel et al., 2000 Lar-roque, 1992 Lundsberg et al., 1997 Parazzini et al., 2003). Subject to the question of the accuracy of self-reported information on...

Allele Frequency

One possible reason for a genetic influence on racial disparities in preterm birth is that susceptibility variants may be present in one population but absent in others or may vary in frequencies across diverse populations. This may affect the number of individuals at increased risk for preterm birth. One obvious example is the unequal distribution of disease-associated alleles for certain recessive disorders, such as sickle cell disease or Tay-Sacks disease. One study examined a total of 179...

Animal Models For Preterm Birth And Neonatal Sequelae

Although most animal species do not have significant rates of spontaneous preterm birth, there is much interest in the use of relevant animal models to elucidate the mechanisms of preterm birth and the neonatal sequelae of prematurity and to develop rationale and efficacious treatment and prevention strategies. However, in choosing an appropriate animal model, a necessary caveat is that many species differ from humans in the length of gestation and the number of fetuses, the type of...

Animal Models of Preterm Birth

Spontaneous preterm birth occurs infrequently in most species. This has limited research in this area to specific pharmacological or environmental interventions that result in preterm birth. Pharmacological administration of RU-486, a progesterone antagonist, leads to preterm delivery in rodents but not in nonhuman primates (Dudley et al., 1996 Garfield et al., 1987 Ha-luska et al., 1994). Administration of cortisol (Grigsby et al., 2000) or maternal starvation (protein and caloric restriction)...

Approach To The Problem

Three themes repeatedly emerged at the start of the committee's deliberations that helped to organize the committee's thinking and approach to this problem. The first was a need for clarity of terminology. In the literature, terms characterizing the duration of gestation, fetal growth, and maturation have been applied inconsistently and have been used interchangeably. This has made it difficult to interpret the data on the causes and consequences of preterm birth and to evaluate treatments. The...

Auditory System and Hearing

The ear begins to develop at the end of 6 weeks of gestation and is fully developed by 20 weeks if gestation. A response to sound can be demonstrated in fetuses and infants born at 23 and 24 weeks of gestation, and auditory brainstem-evoked responses can be recorded this early in preterm infants (Allen and Capute, 1986 Birnholz and Benacerraf, 1983 Starr et al., 1977). The shape of the waveform changes and the conduction time decreases with increasing gesta-tional or postmenstrual age. One to...

Behavioral Influences On Preterm Birth

A special interest in behavioral influences on preterm birth is well justified, given that these are subject to change and could reduce the frequency of preterm birth directly. As previously reviewed in some detail (Berkowitz and Papiernik, 1993 Savitz and Pastore, 1999), a large number of observational studies of a range of health behaviors, including tobacco and alcohol use, nutrition, and physical activity, have been conducted. Although each of these behaviors poses specific challenges in...

Biophysical Predictors

The detection of uterine contractions through maternal self-perception (Mercer et al., 1996) and electronic monitoring (Iams et al., 2002 Main et al., 1993 Nageotte et al., 1988) has been studied to predict preterm delivery. The threshold number of contractions most often studied is four per hour. An increased frequency of self-reported contractions is associated with preterm delivery before 35 weeks of gestation in both nulliparous women (RR 2.41 95 percent confidence interval CI 1.47 to 3.94...

Birth Rates

The significance of the racial and ethnic differences of human populations is frequently debated in clinical, epidemiological, and molecular research (Ioannidis et al., 2004). The undeniable evidence of health disparities between individuals of different races and ethnicities indicates that in some cases a correlation exists between race and health or disease. However, this relationship is complex and poorly understood. First, it is essential to point out that there are no generally agreed upon...

By Use of ART

The Centers for Disease Control and Prevention (CDC) defines ARTs as procedures in which the egg and the sperm are handled in the laboratory, including in vitro fertilization (IVF) as well as related procedures, such as intracytoplasmic sperm injection (ICSI) and gamete intrafallopian transfer (GIFT) or zygote intrafallopian transfer (ZIFT) (Table 5-2). Since 1996, the federal government has mandated that all clinics performing procedures involving ARTs report their outcomes to the CDC (Meis et...

Carbon Monoxide Nitrogen Oxides and Ozone

The relationship of the rates of preterm birth to exposure to carbon monoxide, nitrogen oxides, and ozone pollution is less certain. Exposure to carbon monoxide in ambient air in the last month of pregnancy was associated with preterm birth in a population of women in Vancouver, British Columbia, Canada (Liu et al., 2003), with an adjusted OR of 1.08 (95 percent CI 1.01 to 1.15) for each 1.0-part-per-million increase in the carbon monoxide level. In contrast, the relationship between carbon...

Cardiovascular System

Preterm infants can experience a variety of cardiovascular disorders, ranging from major morphological defects to dysfunctional autoregulation of blood vessels (hypotension). By embryonic day 20, the cells that will form the heart begin to differentiate (Maschoff and Baldwin, 2005 Schultheiss et al., 1995). The primitive heart beats by 4 weeks of gestation and is fully formed at the end of the 6th week. Because gas exchange occurs in the placenta, most of the fetal blood flow bypasses the lungs...

Challenges in Building a Sustainable Research Enterprise

Research progress on preterm birth and infants born preterm will require scientists from many disciplines working in concert. Physician scientists from obstetrics and gynecology are an important component of such teams. What is needed is a paradigm shift in the field of obstetrics and gynecology to provide clinical investigators who can translate the research findings that come from basic science laboratories or pharmaceutical companies into new clinical diagnostic and treatment knowledge. The...

Chlorination Disinfection Byproducts

Because of the widespread use of chlorination as a means to disinfect drinking water supplies, there is considerable interest in the potential health risks from the by-products that are formed because of chlorination disinfection. The principal by-products are trihalomethanes (e.g., chloroform, bromodichloromethane, and dichlorobromomethane), haloacetic acids (e.g., trichloroacetic acid and dichloroacetic acid), and Studies of the health effects of chlorination disinfection by-products are...

Chronic and Catastrophic Stress Exposures

A second set of studies involved a common chronic stressor, such as being imprisoned (Hollander, 2005) or homeless (Stein et al., 2000) during pregnancy or experiencing a catastrophic event occurring during pregnancy (Glynn et al., 2001 Lederman et al., 2004). For example, Lederman and colleagues (2004) assessed the impact of the time of gestation at the time of the World Trade Center terrorist attack on September 11, 2001, among 300 nonsmoking women in New York City who were pregnant at the...

Community Factors

In general, the risks for preterm birth have been individualized that is, those characteristics of individuals that increase the likelihood of preterm delivery within groups rather than the environmental and social factors that affect the rates of preterm birth among the population as a whole (Goldenberg et al., 1998) are emphasized. However, as discussed in Chapter 3 and the previous section on sociodemographic factors, observational studies do not consistently demonstrate strong associations...

Complications for Near Term or Late Preterm Infants

For many years, attention has focused on high-risk obstetric and neonatal intensive care for extremely preterm infants and infants born at the lower limit of viability, although very little attention has been paid to the majority of preterm infants who are born near term (also called late-preterm infants). Although many deliveries of near-term infants are spontaneous or are indicated for maternal or fetal circumstances, it is important to keep in mind that these larger preterm infants born near...

Complications Of Preterm Birth

Developmental immaturity affects a wide range of organ systems. This section describes the short-term complications of preterm birth in terms of fetal development as well as injury to fragile organ systems during the perinatal and neonatal periods. Many of these complications have lifelong consequences for the health, growth, and development of infants born preterm. As described in Chapter 6, the complex interplay of the mechanisms involved in preterm delivery, including inflammation and...

Conclusion

The overall high rate of preterm birth in the United States and the persistent racial-ethnic gap is one of the most significant public health problems today. Despite many years of observational and clinical research, the exposures that place women at risk are not well understood. The substantial intergroup as well as intragroup variabilities in the risk of preterm birth have been shown to be related related to socioeconomic condition, nativity, acculturation, or other maternal characteristics....

Conclusions

Although the mortality rate for preterm infants and the gestational age-specific mortality rate have dramatically improved over the last three to four decades, preterm infants remain vulnerable to the many complications of prematurity. Infants born at the lower limit of viability have the highest mortality rates and the highest rates of all complications of prematurity. Few studies have reported mortality and morbidity rates in gestational age-specific categories, which limits the information...

Conduct Clinical and Health Services Research Investigations

Improve the Methods of Identifying and Treating Women at Risk for Preterm Labor In the past 30 years, important strides in obstetric and neonatal tertiary care have been made to reduce the rates of infant morbidity and mortality as a result of preterm birth. However, the primary and secondary interventions implemented to date have not reduced the rate of pre-term birth. Current prenatal care is focused on risks other than preterm birth. Birth defects, adequate fetal growth, preeclampsia,...

Conduct Etiologic and Epidemiologic Investigations

The committee highlights three specific research areas pertaining to the etiology and epidemiology of preterm birth investigations that will provide an understanding of the etiology of preterm birth, studies of multiple risk factors, and studies that will provide a better understanding of the racial-ethnic and socioeconomic disparities in the rates of preterm birth. 1. Investigate the Etiologies of Preterm Birth The committee finds that the lack of success of public health and clinical...

Costofillness Methodology Applied To Preterm Birth

The societal costs associated with illness are conventionally broken down into direct and indirect costs. Direct costs include the value of the resources used to treat the condition, such as medical care, special education, and developmental services. Indirect costs include the value of resources lost to society, such as the reduced labor market productivity or the reduced level of household productivity due to heightened morbidity or premature mortality. Costs are incremental relative to...

Costs of Preterm Birth

Lion in 2005, or 51,600 per infant born preterm. The share that medical care services contributed to the total cost was 16.9 billion ( 33,200 per preterm infant), or about two-thirds of the total cost, with more than 85 percent of that medical care delivered during infancy. Maternal delivery costs contributed another 1.9 billion ( 3,800 per preterm infant). Special education services associated with a higher prevalence of four disabling conditions (cerebral palsy, mental retardation, hearing...

Definition Of Preterm Birth

The World Health Organization (WHO) has defined preterm birth as delivery before 37 completed weeks of gestation. By convention, gestational age is reported in terms of completed weeks (i.e., one never rounds gestational age up, so 36 weeks and 6 days of gestation is 36 weeks and not 37 weeks of gestation). This definition makes the distinction between being born early and being born too small. Determining when natural conception takes place is difficult (see below), so birth weight (not...

Definition of Preterm Birth Phenotypes

Despite considerable research efforts, limited progress has been made in understanding the etiology of preterm birth. One important problem is the definition of the preterm birth pheno-types. The current approaches for defining and assessing preterm birth phenotypes are inadequate for etiological research and for making the optimal use of genomic data. Most previous studies have relied exclusively on the conventional definition of preterm birth (less than 37 weeks of gestation). Cases of...

Diagnosis And Treatment Of Preterm Labor

The methods for the diagnosis and treatment of preterm labor are based on an inadequate literature that is compromised not only by the oft-cited paucity of well-designed and adequately powered clinical trials but also, even more, by an incomplete understanding of the sequence and timing of events that precede clinical evidence of preterm labor, such as progressive cervical dilatation and ruptured membranes. Because the progression from subclinical preterm parturition to overt preterm labor is...

Disability in Late Preterm or Near Term Infants

The rates of mortality (discussed in Chapter 10) and neurodevelopmental disability for moderately preterm infants, that is, those born between 32 and 36 weeks gestation or those weighing 1,500 to 2,499 grams at birth, are higher than those for infants born full term (although they are lower than those for infants born more prematurely). Although children born between 32 and 36 weeks of gestation comprise only about 8 to 9 percent of all births, they account for 16 to 20 percent of children with...

Disparities in Infertility Treatment

As discussed in Chapter 4, socioeconomic differences in multiple gestations have not been well studied (Kramer et al., 2000). The literature on infertility, utilization of treatment, and outcomes of treatment has been focused on white and socieconomically advantaged populations. While the extent to which various racial-ethnic minority populations and subpopulations experience fertility problems is not precisely known , a series of recent reports developed from a workshop, Health Disparities in...

Douching Before and During Pregnancy

A number of indirect lines of evidence suggest that the practice of vaginal douching might increase the risk of preterm birth. Douching is a common behavior and is more common among African-American women than white women, consistent with the increased prevalence of bacterial vaginosis (BV) and preterm birth among African-American women (Bruce et al., 2000). Furthermore, douching alters the vaginal microflora and may well facilitate the passage of vaginal pathogens to the upper reproductive...

Early Intervention Services

Evidence from Massachusetts on early intervention (EI) services delivered between the first through third years of life suggests that the rate of provision of such services for preterm infants is significantly higher on a per-case basis than that for term infants. Mean expenditures for such services per case displayed an inverse gradient by gestational age less than 28 weeks, 7,182 28 to 30 weeks, 5,254 31 to 33 weeks, 2,654 34 to 36 weeks, 1,321 and 37 to 39 weeks, 697 (Clements et al., 2005)....

Economic Evaluation Of Interventions To Reduce Preterm Birth And Its Consequences

Economic evaluation of interventions that can be used to reduce the rates of preterm birth and its adverse consequences can aid in decision making regarding the development and integration of new technologies and programs. The techniques for such an evaluation take on several different forms. Cost identification assesses the burden of illness and the features of its distribution in economic terms, as with the estimates provided above. Such estimates can form part of the foundation for the...

Education

Through the Individuals with Disabilities Education Act (IDEA which was renewed in 2004) (DOE, 2005), children with long-term health conditions receive a variety of services. The original legislation underlying these programs called for assuring the free appropriate public education in the least restrictive environment. The two main IDEA programs include early in tervention services and special education. Early intervention services cover children from birth to 3 years of age, at which point...

Evidence Of Genetic Influences On Preterm Delivery

The available literature has provided some evidence of familial and intergenerational influences on low birth weight or preterm birth (Bakketeig et al., 1979 Carr-Hill and Hall, 1985 Khoury and Cohen, 1987 Porter et al., 1997 Varner and Esplin, 2005). A population-based cohort study of data from birth certificates and fetal death certificates from the state of Georgia between 1980 and 1995 suggest that the recurrence of preterm delivery contributes to a notable portion of all preterm births,...

Exposure Assessment Challenges

A variety of approaches have been used to estimate exposures and to investigate the associations between environmental chemical exposures and preterm birth. A common approach has been to use employment or location of residence as a proxy for exposure, such as working with pesticides, proximity to a pollution source, or residence in a polluted locality. In those studies, exposure is typically estimated from measurement of the levels of contamination of common environmental media, such as...

Family Costs Maternal Costs

Several studies have estimated the excess maternal costs associated with the birth of an LBW infant and with preterm birth (Zupancic, 2006). Most such studies focused strictly on elevated delivery costs, although two recent U.S. studies incorporated prenatal hospital admissions as well (Gilbert et al., 2003, Schmitt et al., 2006). One study included any subsequent transfers until the mother was ultimately discharged (Gilbert et al., 2003). Use of the estimates from the IHC cohort data used...

Family History and Spontaneous Preterm Birth

Several observations support the hypothesis that spontaneous preterm birth is influenced by a family history of preterm birth. First, evidence from two studies performed with twins suggests a genetic predisposition for preterm birth with estimates of the proportion of preterm births among women with a family history of preterm birth ranging from 20 to 40 percent (Blackmore-Prince et al., 2000 Fuentes-Afflick and Hessol, 2000). Other observations support the idea that genetic factors affect the...

Funding For Research On Preterm Birth

The primary sources of funding for research on premature birth and individuals who survived preterm birth are NIH, the Centers for Disease Control and Prevention (CDC), and nonprofit voluntary health or philanthropic organizations, such as the March of Dimes and the Burroughs-Wellcome Fund. These agencies and organizations support research related to the basic science of the events that lead to preterm labor, interventions that can be taken to prevent pre-term labor, treatments for infants who...

Geneenvironment Interactions

The goal of gene-environment studies in epidemiology is to advance knowledge of how genetic and environmental factors combine to affect the risk of disease and, more specifically, how the variations in the human genome (polymorphisms) can modify the effects of exposures to environmental health hazards (Kelada et al., 2003). There are compelling reasons to examine the association of gene-environment interactions with preterm birth. The data presented in the previous chapters and in this chapter...

Gene Environment Interactions

Because the constellation of socioenvironmental variables known to affect the risk of pre-term birth is not equitably distributed across racial-ethnic groups, the interaction of these factors with genetic predispositions may also produce highly disparate clinical outcomes. As discussed in the previous section, this area needs to be further investigated. In summary, the question of whether genetics explains a substantial proportion of health disparities in preterm birth, is largely unanswered....

Genetic Effects

Another possible reason for a genetic influence on racial-ethnic disparities in preterm birth rates is the variation in the effect of a given genetic variant between racial groups. However, data that can be used to either support or disprove this hypothesis are limited. One study examined the genetic effects of 43 validated gene-disease associations among 697 study populations of various descents (Ioannidis et al., 2004). The frequencies of the genetic marker of interest in the control...

Growth

Besides acute and chronic conditions, LBW and preterm infants also experience poorer growth. The first three years of life evidence a discrepancy in the growth patterns of children born LBW, compared to those of NBW (Binkin et al., 1988 Casey et al., 1991). Poor growth resulting from intrauterine, neonatal, or postnatal growth failure has been documented widely among children born VLBW (Binkin et al., 1988 Casey et al., 1991). Studies performed with adolescents who were born LBW (less than...

Health And Growth Health

As with much of the literature reviewed in this volume, studies of the health of premature infants after discharge from the hospital have been characterized largely in terms of birth weight. The most frequently cited evidence of a higher risk for adverse health status among low birth-weight (LBW) and preterm infants is an increased risk of rehospitalization during the first few years of life. Infants born weighing 1,500 grams or less are four times more likely than normal birthweight (NBW)...

Health Insurance

Medicaid pays for a large share (40 percent) of the medical costs associated with preterm birth (Russell et al., 2005). Because low-income pregnant women are eligible for Medicaid, Medicaid pays for about a third of all deliveries in the United States (Rosenbaum, 2002). Most children in the United States receive health insurance through a parent's employment. The next most common sources of health insurance for children are the Medicaid program and the State Children's Health Insurance Program...

Health Related Quality of Life

Health, as formulated by the World Health Organization (WHO, 1958) is a 'state' of complete physical, mental and social well-being and not merely the absence of disease or infirmity. Health-related quality of life (HRQL) is a narrower concept that considers the net impact or consequence of a disease or impairment and implicitly reflects the personal values of the individual (Gill and Feinstein, 1994). Measurement of HRQL can be used for comparisons with different disease conditions, as well as...

Hearing Impairment

Data on the incidence of hearing loss in preterm infants are conflicting (Table 11-4). A number of studies of children born preterm with birth weights of less than 1,000 grams reported a 9 to 14 percent incidence of hearing impairment, whereas nine other studies reported an incidence similar to that in controls who had been born full term (1 to 2 percent) (AHRQ, 2002). A Swedish study of 18- to 19-year-olds born between 1973 and 1975 with birth weights of less than 1,500 grams found impaired...

Priority Areas for Research Better Define the Problem of Preterm Birth with Improved Data

The concept of prematurity involves biological immaturity for extrauterine life. Maturation is the process of achieving full development or growth. Infants born preterm have immature organ systems that often need additional support to survive. The degree of maturity, therefore, is the major determinant of mortality and morbidity (the short- and long-term complications) of preterm birth. Accurate definitions of preterm birth are essential for comparing and interpreting the various studies that...

Study and Inform Public Policy

Because preterm birth is concentrated in populations of low socioeconomic status, the cost of preterm birth generates a considerable burden on public programs, many of which target low-income and other vulnerable populations. As noted above, pregnant women who have received ART may not be representative of all pregnant women (among other things, evidence suggests that they are from socioeconomically advantaged backgrounds). Thus, this fact should be taken into account when generalizations are...

Priorities Areas for Research

Better define the problem of preterm birth with improved data Recommendations included in this category pertain to the need for improved collection of surveillance and descriptive data in order to better define the nature and scope of the problem of preterm birth. 2. Study the economic outcomes for infants born preterm Conduct clinical and health services research investigations Recommendations in this category pertain to the need to examine and improve the clinical treatment of women who...

Implantation Errors

Traditionally, preterm delivery was thought to result from events that occurred at about the time of labor onset. The finding of elevated CRH levels before midgestation in association with preterm delivery suggests that some events triggering preterm delivery may be set in motion earlier in pregnancy than was previously thought (Hobel et al., 1999 Leung et al., 1999 McLean and Smith, 1999 McLean et al., 1999). A growing body of evidence now suggests that complications that become apparent...

Implications For Public Health And Research

Although the complex interplay between the duration of pregnancy, fetal and infant size and maturity, and how they are measured are sources of some confusion, evaluation of the interrelationships among these factors provides an opportunity to gain some insight into the factors contributing to preterm birth. For example, racial disparities in all aspects of health have long been recognized, and the causes of these disparities are poorly understood. Public health databases with data on births,...

Infertility Treatments And Preterm Birth

Infertility treatments have allowed thousands of couples who have difficulty conceiving to fulfill their desire to have children. In the United States in 2002, 7.3 million women, or 12 percent of women ages 15 to 44, had physical difficulty becoming pregnant or carrying a baby to term. Approximately 2.1 million of these women, or 7 percent of all women between the ages of 15 and 44, were infertile, defined as not becoming pregnant after 12 months when the couple is not using contraception (CDC,...

Info

FIGURE 1-7 Percentage of live births from ART by maternal age, 2002. SOURCE NCCDPHP (2005). In addition to the health problems associated with preterm birth described at the outset of this chapter, preterm birth is accompanied by broad emotional and financial costs and lost opportunities for families. The birth and hospitalization of preterm infants are associated with maternal distress (Eisengart et al., 2003 Singer et al., 2003) and maternal depressive symptoms (Davis et al., 2003)....

Information Informing Decisions Surrounding Perinatal Interventions

Obstetricians are taught that their first obligation and priority is the mother's health but that women and families are willing to accept some degree of increased risk to the mother if it will benefit her fetus (see Appendix C for a discussion of ethical issues). A decision to arrest pre-term labor may increase the risk to both the mother and the fetus if the pregnancy is complicated by bleeding, hypertension, or infection. A lesser risk usually attends uncomplicated preterm labor but...

Introduction

The period of gestation is one of the most important predictors of an infant's subsequent health and survival. In 2004, more than 500,000 infants, or 12.5 percent of all infants, were born preterm, which is considered birth at less than 37 completed weeks of gestation (CDC, 2005a). On the basis of new estimates provided in this report, the annual societal economic burden associated with preterm birth in the United States was in excess of 26.2 billion in 2005 (this estimate represents a lower...

Kangaroo Care

Kangaroo care provides skin-to-skin care by placing the naked preterm infant in an upright position between the mother's breasts and allows unlimited breast-feeding. This concept of caring for preterm infants originated in Bogota, Columbia, as a low-cost way to assist preterm infants with temperature regulation, nutrition, and stimulation (Charpak et al., 1996). Kangaroo care is initiated after a routine period of stabilization after birth. A number of studies from developing countries,...

Late Term or Near Term Infants Born at the Upper Border of Prematurity

At all times during a pregnancy, accurate dating of the pregnancy and accurate estimates of fetal maturity provide better information for decision making by the health care provider and the family. Although this is especially true for the high-risk pregnancies noted above, the information also assists the health care provider and the family with making decisions on the how a threatened preterm delivery is managed and the optimal timing and mode of delivery as a pregnancy approaches fullterm....

Liability Issues

Obstetricians and gynecologists are charged significantly higher premiums for liability insurance than physicians in other specialties (MacLennan et al., 2005). When clinical departments must pay 150,000 or 165,000 a year for a faculty member's malpractice insurance, as they are in Pennsylvania and Alabama, respectively, it absorbs resources that might otherwise be available to support research. The AAMC Report on Medical School Faculty Salaries, 2003-04 (AAMC, 2005) shows that the mean...

Life Events

Life events are major events that individuals experience, such as divorce, a death in the family, illness, injury, or the loss of a job (Cohen et al., 1995). Eight studies assessed life events and tested whether a count of the number of events occurring during pregnancy or the severity or the impact of those events predicted preterm birth. Three obtained nonsignificant results, including one large prospective study (Goldenberg et al., 1996a), one prospective study with a small sample size...

Location of Residence

Several studies found that women who live in an area with high levels of air pollution are more likely to deliver preterm than women who live in less polluted areas. Women who live near petroleum refinery plants (Lin et al., 2001 Yang et al., 2004a), petrochemical industrial complexes (Yang et al., 2002a,b), or industrial districts with increased levels of emission of air contaminants from multiple sources (including petrochemical, petroleum, steel, and shipbuilding industries) (Tsai et al.,...

Maternal

Several studies have identified young maternal age as an important risk factor for preterm birth (Amini et al., 1996 Branum and Schoendorf, 2005 Copper, 1995 Fraser et al., 1995 Hediger et al., 1997 Satin et al., 1994 Scholl et al., 1992, 1994). Hediger et al. (1997) found that young adolescents (less than 16 years of age at the time of their last menstrual period), especially those of young gynecological age (within 2 years of menarche), had a twofold greater risk for preterm delivery compared...

Measurement Of Fetal And Infant Maturation

Although much attention has been paid to accurate obstetric estimates of gestational age, there is a similar need for more methods of assessment of fetal and infant maturity. The assessment of maturity is even more important when the gestational age of the fetus is unknown or uncertain. For most preterm infants, the most important determinant of their survival, the development of complications, health sequelae, and neurodevelopmental outcome is the infant's degree of maturation at birth...

Measures of Fetal Lung Maturity

In the 1970s, obstetricians began to analyze chemically the amniotic fluid surrounding the fetus to measure fetal lung maturity (Gluck and Kulovich, 1973 Gluck et al., 1971, 1974 Philip and Spellacy, 2004 Spellacy and Buhi, 1972). The respiratory distress syndrome associated with immature lungs is due in part to the deficient production of surfactant, which stabilizes the alveoli (air sacs) (Chapter 10). With fetal breathing, surfactant is dispersed into the amniotic fluid. Gluck (1971) and...

Measures of Functional Maturity

Neuromaturational changes in brain structural and functional development have been noted in preterm infants. These changes can be detected by detailed neurological examination, neuroimaging (especially cranial ultrasound), electroencephalography (EEG), amplitude-integrated EEG (a-EEG), electroretinography and neurophysiological measures of conduction time after auditory, visual, or tactile stimulation (Finnstrom, 1972 Miller et al., 1983 Henderson-Smart et al., 1985 Kesson et al., 1985 Klimach...

Methodological Issues in Modeling Social Context

The inclusion of social conditions in models of cumulative risk depends on the ability to validly measure the various components of social context at appropriate scales of influence. In their simplest form, multilevel studies typically include assessments at the individual and community levels by the use of some standard administrative unit to define community (e.g., health area, zip code, census tract, or block). For example, exposure to poverty or substandard housing may be measured at the...

Mortality

Infants born preterm are more likely than infants born full term to die during the neonatal period (first 28 days) and infancy (first year), and mortality rates increase proportionally with decreasing gestational age or birth weight (Alexander et al., 1999 Allen et al., 2000 Lemons et al., 2001 Martin et al., 2005) (see also Figures 9-2 and 9-3 in Chapter 9 and Appendix B). The leading causes of infant mortality in the United States are preterm birth, low birth weight, and birth defects so...

Neonatal Individualized Developmental Care and Assessment Program

Als devised a highly organized comprehensive system for providing neurodevelopmental support in a NICU (Als, 1998). This system, commonly known as NIDCAP, has generated much interest and is often equated with NICU developmental care (Ashbaugh et al., 1999). Its systematic implementation requires development of NICU developmental care teams with dedicated staff trained and certified in NIDCAP, the systematic observation of the behavior of the infants, the coordination of care, and careful...

Neonatal Lung Disease

The premature infant faces primarily two lung-related injuries acute injury (respiratory distress syndrome RDS ) and chronic or progressive lung injury (bronchopulmonary dysplasia BPD ) (also see Chapter 10 for a discussion). A complex interplay of factors plays into the risk of these injuries, including incomplete development (immaturity), mechanical ventilation, oxida-tive stress, and inflammation (Zoban and Cerny, 2003). Neonatal RDS is an acute lung process due to a deficiency in...

Neurodevelopmental Disabilities

Among the earliest concerns about the health of premature infants was the association between preterm delivery and neurodevelopmental disabilities. Neurodevelopmental disabilities are a group of chronic interrelated disorders of central nervous system function due to malformation of or injury to the developing brain. The spectrum of neurodevelopmental disabilities includes the major disabilities cerebral palsy (CP) and mental retardation. Sensory impairments include visual impairment and...

Nonmedical Interventions

Nonmedical interventions, such as social support, reduction of stress, improved access to prenatal care, and reduced physical activity, can be used to reduce the rates of preterm birth and were reviewed in Chapter 3. A recent study examined the rates of low birth weight among participants in a Medicaid-funded prenatal program for high-risk women (Ricketts et al., 2005). The results indicated that the infants of women who stopped smoking had a rate of low birth weight of 8.5 percent, whereas the...

Other Prophylactic Medications

Studies of the use of tocolytic agents as prophylaxis for preterm birth have shown no evident benefit (Berkman et al., 2003 King et al., 1988 Sanchez-Ramos et al., 1999). Evidence that the parturitional process begins well in advance of coordinated uterine activity (Challis et al., 2000) may explain the inability of contraction suppression to prevent preterm birth in randomized trials. Investigations summarized and reanalyzed by Keirse (1990) suggested that supplemental administration of...

Pain and Discomfort

The relationships between frequent or chronic pain, the stress response, cortisol levels, and the neurodevelopment of the preterm infant are extremely complex (Grunau, 2002 Clin Perinatol 29 373 Grunau et al., 2006 Seminars in Perinatology in press). The fetus or preterm infant responds to painful stimuli with increases in cortisol and endorphin levels as early as 23 weeks of gestation, but the neurotransmitters that attenuate pain develop later in postnatal life (Anand, 1998 Biol Neonate 73 1...

Paternal Exposures To Environmental Toxicants

A few studies have considered the role of toxicant exposures of the father in preterm birth. Each of these studies involved exposures in the workplace. Two studies of Norwegian historical occupational records examined the role of paternal occupational exposure and preterm birth. In the first study, paternal employment in the printing industry, which results in increased occupational exposure to lead and solvents, was not associated with preterm birth of less than or equal to 37 completed weeks...

Personal Resources

The emerging literature on personal resources warrants attention in multilevel research attempts to understand preterm birth better. The term personal resources refers to individual differences in views about one's self and the world, such as self-esteem, mastery, perceived control, and optimism. These are conceptualized as relatively stable characteristics of individuals that are generally protective of the individual' s health and that function as coping resources (Lachman and Weaver, 1998...

Physiological Severity Measures

The number, type, and severity of complications of prematurity are directly proportional to neonatal immaturity and physiological instability. Early markers of immaturity or physiological instability would alert health care providers to anticipate other complications and take actions to prevent or treat them as early as possible. Several measures of severity of acute illness (e.g., Scoring for Neonatal Acute Physiology and Clinical Risk Index for Babies) have been developed and are associated...

Polychlorinated Biphenyls

Polychlorinated biphenyls (PCBs) are industrial chemicals that were manufactured and used commercially as mixtures of congeners, with each congener distinguished by the number and pattern of chlorination of the biphenyl rings. Certain PCB congeners persist in the environment, are poorly metabolized, and biomagnify in the food chain. These characteristics result in increased opportunities for human exposure. The production and commercial use of PCBs were discontinued in most countries in the...

Postnatal Estimates of Maturity

In the 1960s to 1970s, missing or inaccurate gestational age data for many newborns led to a search for postnatal methods of determining gestational age. These methods invariably focused on the degree of infant maturation (Allen, 2005a Philip et al., 2003). Farr et al. (1966) described the maturation of a number of external physical characteristics in preterm and term infants. Hittner et al. (1977, 1981) proposed a systematic method of grading the disappearance of the pupillary membrane (i.e.,...

Postnicu Discharge Interventions

In recognition of the increased developmental and emotional risks for children born pre-term, several interventions have focused on the provision of services in the early years of life to prevent subsequent developmental and health problems. Coordinated, community-based, multid-isciplinary programs for early intervention, based on the findings of some seminal studies, have been established for children and their families. The types and severities of the conditions affecting children with...

Potential Mechanisms of PPROM

The fetal membranes (amnion and chorion) abut the maternal decidua and rest upon a collagenous basement membrane of type II and IV collagen. Beneath this layer is a fibrous layer that contains collagen types I, III, V, and VI. Thus, collagen provides major structural strength for the membranes. Membrane rupture is a process similar to wound healing, a process in which collagen is degraded (Malak and Bell, 1994). MMPs are the only family of enzymes that act to degrade collagen and play a major...

Prediction And Assessment Of Risk Of Preterm Birth

The rationale for prediction of spontaneous preterm birth is threefold. First, by delineating factors predictive of preterm birth, the mechanisms and biological pathways that lead to spontaneous preterm parturition may be better understood. Second, the use of predictors of spontaneous preterm birth permits identification of a group of women at the highest risk for whom an intervention may be tested and for whom intervention is most needed. The third motivation for prediction of spontaneous...

Preterm Birth

Preterm birth occurs disproportionately in populations of low socioeconomic condition. Because many public programs target these populations, the costs of preterm birth to the public are substantial. For example, 40 percent of preterm births are paid for by Medicaid (Russell et al., 2005). The costs of preterm birth, however, extend far beyond the medical costs associated with birth. As has been documented in previous chapters, preterm birth has significant lifetime consequences for many...

Prevention Strategies

The prevention of preterm birth has been attempted by the use of interventions aimed at each of the risk factors described in the previous chapters, largely without success (Table 9-5). TABLE 9-5 Summary of Studies of Medical Interventions to Prevent Preterm Birth tion Studied Interventions Tested in RCT Outcome Nutritional supplements Vitamins C and E No benefit, vitamin C-CPEP Trial, inadequate data Prior preterm birth and bacterial vagi-nosis Antibiotics during pregnancy Mixed results...

Productivity

Lost labor market and household productivity for individuals born preterm may result from disabling conditions, from the more subtle effects of cognitive or behavioral deficits, or from lower intelligence quotients. Lost productivity can result from either premature mortality or heightened morbidity, in which the ability to work or the amount of work, or both, could be affected. One complication for the calculation of indirect mortality and morbidity costs that is generally ignored when infant...

Proteomics

Despite the many advantages and advances in knowledge attributable to genomics and mi croarray analysis, these approaches have several limitations. Although the human genome contains approximately 30,000 genes, many more messenger RNA transcripts potentially coding for different proteins exist because of the alternate splicing of genes. Depending on codon bias, there is only a limited relationship between the expression of a gene and the amount of protein expression directed by that gene. The...

Psychosocial Factors And Preterm Birth

In 1985 the Institute of Medicine (IOM) issued a report on low birth weight that concluded that stress was one promising avenue for future research (IOM, 1985). Since then, the findings of many more investigations have been published, as have numerous reviews, partial reviews, and commentaries on this area of research (Istvan, 1986 Lederman, 1986 Lobel, 1994 Kramer et al., 2001 Paarlberg et al., 1995 Savitz and Pastore, 1999). However, existing reviews are outdated because of the burgeoning of...

Public Policies Affected by Preterm Birth

Because many public entitlement and benefit programs target minority individuals and individuals of low socioeconomic condition, who are at increased risk of delivering infants pre-term, the burden of illness associated with preterm birth falls disproportionately on the public sector. The consequences of preterm birth have implications not only for medical costs but also for a broader range of services and social programs, such as early intervention programs, special education, income support...

Racial and Ethnic Disparities

Although controversy exists over inclusion criteria for racial and ethnic subgroups, racial and ethnic disparities in preterm birth rates, birth weight distributions for gestational age, neonatal and infant mortality rates, and gestational age- and birth weight-specific neonatal mortality rates have been consistently reported (see Appendix B). In the United States in 2003, preterm birth rates were 10.5 for Asian and Pacific Islanders, 11.3 percent for whites, and 17.8 percent for African...

Racial and Ethnic Disparities in Preterm Birth

The large disparities in the proportion of preterm births and other birth outcomes between racial and ethnic groups in the United States have been persistent and troubling. The categorization of racial and ethnic groups is difficult and controversial because there is no simple method for defining these groups or subgroups. However, it is important to collect data on race and ethnicity to document and assess health status and health outcomes for various groups of the U.S. population. The U.S....

Racial Disparities In Environmental Exposures

As discussed more extensively elsewhere in this report, preterm births are more prevalent among African-American women than among women of other racial-ethnic groups, and this pattern has persisted over the years. The terms environmental justice and environmental racism describe the disproportionate burden of environmental pollution on poor and minority populations (Brown, 1995 Silbergeld and Patrick, 2005). A recent review by Silbergeld and Patrick (2005) discusses in detail the...

Recommendation II1 Support research on the etiologies of preterm birth Funding

Agencies should be committed to sustained and vigorous support for research on the etiologies ofpreterm birth to fill critical knowledge gaps. Areas to be supported should include the following The physiological and pathologic mechanisms of parturition across the entire gesta-tional period as well as the pregestational period should be studied. The role of inflammation and its regulation during implantation and parturition should be studied. Specifically, perturbations to the immunologic and...

Recommendation II5 Institute guidelines to reduce the number of multiple gestations

American College of Obstetricians and Gynecologists, the American Society for Reproductive Medicine, and state and federal public health agencies should institute guidelines that will reduce the number of multiple gestations. Particular attention should be paid to the transfer of a single embryo and the restricted use of superovulation drugs and other nonassisted reproductive technologies for infertility treatments. In addition to mandatory reporting to the Centers for Disease Control and...

Recommendation III1 Improve methods for the identification and treatment of

Women at increased risk of preterm labor. Researchers should investigate ways to improve methods to identify and treat women with an increased risk of preterm labor. The content and structure of prenatal care should include an assessment of the risk of preterm labor. Improved methods for the identification of women at increased risk of preterm labor both before pregnancy and in the first and second trimesters are needed. Combinations of known markers of preterm labor (e.g., a prior preterm...

Recommendation IV1 Develop guidelines for the reporting of infant outcomes

National Institutes of Health, the U.S. Department of Education, other funding agencies, and investigators should develop guidelines for determining and reporting outcomes for infants born preterm that better reflect their health, neurodevelopmental, educational, social, and emotional outcomes across the life span and conduct research to determine methods that can be used to optimize these outcomes. Outcomes should be reported by gestational age categories, in addition to birth weight...

Recommendation V1 The National Institutes of Health and private foundations

Should establish integrated multidisciplinary research centers. The objective of these centers will be to focus on understanding the causes of preterm birth and the health outcomes for women and their infants who were born preterm. Consistent with the Roadmap initiative of the National Institutes of Health, these activities should include the following Basic, translational, and clinical research involving the clinical, basic, and behavioral and social science disciplines is needed. This...

Recommendation V2 Establish a quality agenda Investigators professional societies

State agencies, payors, and funding agencies should establish a quality agenda with the intent of maximizing outcomes with current technology for infants born preterm. Define quality across the full spectrum of providers who treat women delivering pre-term and infants born preterm Identify efficacious interventions for preterm infants and identify the quality improvement efforts that are needed to incorporate these interventions into practice and Analyze variations in outcomes for preterm...

Recommendations

The committee finds that the lack of success of public health and clinical interventions to date is due, in large measure, to the limited understanding of the heterogeneous etiologies of preterm birth. Recommendation II-1 Support research on the etiologies of preterm birth. Funding agencies should be committed to sustained and vigorous support for research on the etiologies ofpreterm birth to fill critical knowledge gaps. Areas to be supported should include the following The physiological and...

Research And Policy

Recommendation V-1 The National Institutes of Health and private foundations should establish integrated multidisciplinary research centers. The objective of these centers will be to focus on understanding the causes of preterm birth and the health outcomes for women and their infants who were born preterm. Consistent with the Roadmap initiative of the National Institutes of Health, these activities should include the following Basic, translational, and clinical research involving the clinical,...