PRETERM DELIVERY

March of Dimes Updates

Taking action against prematurity

From the March of Dimes Birth Defects Foundation

In January, the March of Dimes launched a 5-year, $75 million national campaign targeting the complex problem of prematurity. Since we don't know what causes approximately half of all spontaneous preterm births, impacting prematurity is a formidable challenge. Obstetrical providers have a pivotal role in meeting this stubborn challenge.

US trends in preterm delivery

Over the past two decades, the rate of preterm delivery (PTD)—live birth prior to 37 completed weeks' gestation—has increased in the United States from 8.9% in 1980, to 10.6% in 1990 and to 11.6% in 2000. Between 1998 and 2000 the PTD rate plateaued around 11.6%, reflecting more than 467,000 preterm births annually (Figure 1). The overall increase in PTD is due to an increase in the rates of moderately preterm births (32 to 36 weeks' gestation), which accounted for 8.7% of all births in 1990 and 9.7% in 2000—an 11% increase over the decade. The rates of very preterm births (<32 weeks) did not change, remaining at 1.9%. A parallel trend has been observed for incidence of low birthweight—defined as less than 2,500 g—which has increased from 6.8% in 1980 to 7.0% in 1990 and to 7.6% in 1998, where it has remained through 2000 (Figure 2). These LBW rates correspond to more than 300,000 LBW births annually.

As with most perinatal outcomes, there are substantial disparities in preterm rates by race and ethnicity, underscoring the necessity of targeting the groups with the highest rates to impact on the problem of prematurity (Figure 3). The majority of the approximately 4 million annual live births in the nation are to non-Hispanic white women, however, so the total number of preterm births is greatest in this group, constituting more than half of all such deliveries (Figure 4).

Prematurity/low birthweight and perinatal mortality

Prematurity/low birthweight continues to be responsible for about 75% of perinatal mortality (fetal deaths and deaths within the first 6 days of life). For the first time, in 1999, this became the leading cause of neonatal mortality (deaths in the first month of life), surpassing birth defects. Prematurity/low birthweight is also the second leading cause of infant mortality (deaths within the first year of life) in the US, and for more than a decade, it has been the number one cause of black infant mortality. In fact, it is the only leading cause of infant deaths in the US for which the rate has increased in the past decade (Figure 5).

Being preterm and/or having low birthweight profoundly increases the risk that an infant will die. This fact underscores the improvements that could be achieved if the births of the earliest and smallest infants could be delayed. For example, in 2000, without the 7.6% of US infants born LBW, the US infant mortality rate (IMR) would have been only 2.5/1,000 live births instead of 6.9/1,000 live births. This would translate into 18,300 fewer infant deaths. Calculated gestational age-specific IMRs attest to the impact of preterm delivery on infant deaths (Table 1).

TABLE 1
Infant mortality rates by gestational age (United States, 2000)

Associated morbidity, disability, and costs

In addition to perinatal loss, prematurity is a major determinant of neonatal, infant, and lifetime morbidity and disability, including cerebral palsy and mental retardation. Half of all long-term neurological disabilities in children are associated with prematurity. Long-term follow-up of neonatal intensive care unit (NICU) graduates suggests that both serious and mild neurodevelopmental, neurosensory, respiratory, gastrointestinal, behavioral, and social problems are more prevalent than previously reported.^1,2

According to a 1995 report, health-care costs for babies born before 37 weeks' gestation, usually at low birthweight, are an average of 10 times higher than the costs for babies born full term. Prematurity/low birthweight accounts for about 35% of all health-care spending on infants and 10% of all health-care spending on children.³ Current cost data are lacking, however, and more research based on enhanced documentation and reporting is needed to fully appreciate the enormous economic impact of preterm birth.

Factors contributing to increases in preterm delivery

In addition to maternal history of preterm labor/delivery, many risk factors have been identified for preterm labor/delivery (Table 2). Multifetal pregnancy and advanced maternal age are two important predictors of preterm delivery and low birthweight. At least half of all twins born in the US will be early and small, and for higher-order multiples (triplets or more), PTD rates now approach 93%.⁴ Both of these risk factors have increased in the past decade, multiple births by 35%, from 2.3% of all births in 1990 to 3.1% in 2000, and births to women aged 35 and older by 53%, from 8.8% of the total in 1990 to 13.5% in 2000. In 2000, more than 5% of births to women aged 35 or older were multiples. While increased multifetal gestations account for a large part of the rise in preterm delivery for white infants, other factors have boosted the overall high rates of preterm births. Some factors that are increasing in parallel with higher PTD rates are a marked increase in inductions and medically indicated deliveries in the US, the increasing incidence and prevalence of asymptomatic bacterial and viral infections, rising obesity rates, and substance abuse (tobacco, alcohol, and illicit drugs).^5-9 While substance abuse during pregnancy has consistently been associated with increased risk of preterm delivery, it is not clear how much of the increase is due to the actual substance and how much to other adverse socioeconomic factors.¹⁰ Research has also identified an important role of maternal and fetal stress, especially if it occurs early in pregnancy and is a type over which the woman has little control, such as the stress associated with catastrophic events, domestic violence, and racism.^11,12

TABLE 2
Maternal factors for preterm labor/delivery

Multifetal pregnancy
Maternal age (<17 and >35 years)
Black race
Low SES
Unmarried
Previous fetal or neonatal death
>3 spontaneous terminations
Uterine abnormalities
Incompetent cervix
Genetic predisposition
Low prepregnant weight
Obesity
Infections
Bleeding
Anemia
Major stress
Lack of social supports
Tobacco use
Illicit drug use
Alcohol abuse
Folic acid deficiency

Primary, secondary, and tertiary prevention of preterm labor/delivery

Most preterm prevention programs have focused on secondary prevention, such as stopping preterm labor once it has started. Growing evidence suggests a low success rate with this approach, which may be too late for the current pregnancy but can improve survival and minimize morbidity. For example, educating all pregnant women about the signs and symptoms of preterm labor can facilitate earlier contact with a health-care provider so that antenatal steroids can be administered. When done in combination with surfactant therapy, it resulted in dramatic decreases in the 1990s in the rates of respiratory distress syndrome (RDS) and other complications, including intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL). These benefits are apparent, provided that clinicians comply with the single-treatment recommendations for antenatal steroids from the 2000 National Institute of Child Health and Human Development (NICHD) conference, unless they are participating in large national network randomized controlled trials.

Other PTD prevention efforts have focused on risk assessment and/or prediction of preterm delivery. But despite creative scoring systems and prediction algorithms, at best they identify about half of preterm deliveries.^13,14 Recent work has improved the usefulness of biomarkers such as fetal fibro-nectin in combination with cervical length. However, while these two tests have excellent negative predictive value, neither has a very high positive predictive value, which would be needed to support secondary prematurity prevention trials. Therefore research in this area needs to continue.¹⁵

Paralleling these prevention efforts, concurrent strategies and interventions are needed that address primary prevention. In particular, a comprehensive, culturally sensitive, age-appropriate risk-reduction approach is needed that targets women and their partners as early as possible. Ideally, risk-reduction obstetric care would be initiated before conception and would continue throughout pregnancy. This approach must address prevention or reduction of exposures to preventable conditions such as unintended pregnancy; all substance abuse; prevention and treatment of infections; assurance that immunizations are up to date; treatment of underlying medical conditions and mental health problems; promotion of optimal weight, exercise and nutrition (including ensuring that everyone age 14 and older take 400 µg of folic acid daily); ways to decrease stress; and assessment of medication, herbal, and environmental exposures.^16,17

Evidence-based interventions

A 1998 review article by Goldenberg and Rouse on the prevention of spontaneous preterm birth summarized those few interventions that were universally applicable to prevent PTD and called for the need to better understand the causes and pathogenesis of PTD.¹⁸ The key message is that much basic and applied clinical research needs to be done. This perspective was followed by a number of recent evidence-based reviews by the Agency for Health Research and Quality (AHRQ) and the American College of Obstetricians and Gynecologists. AHRQ looked at low birthweight and disparities in their LBW Patient Outcomes Research Team (PORT), and in 2000, published the two-volume preterm labor report.^19,20 ACOG has provided many technical and clinical practice bulletins related to PTD, most recently in October 2001 and September 2002.^21,22 Both provide important guidelines for interventions that do and do not work and methods of counseling families about risks for the fetus based on birthweight category and gestational age.

Also last year, Dr. Charles Lockwood called for earlier interventions in an editorial in The New England Journal of Medicine, reminding clinicians that "the prevention of preterm delivery will require interventions at an earlier stage in the process that leads to it."²³ He mentioned the need to prevent ascending infections, rigorously evaluate therapies for women with acquired or inherited thrombophilias, and refine our assisted reproductive technologies to reduce the occurrence of twin and higher-order multifetal pregnancies. He concluded by stating that we have come a long way in understanding the pathogenesis of preterm delivery but cautioned that there is still a long way to go.

Launching the national prematurity campaign

Last month, the March of Dimes began a 5-year, $75 million prematurity campaign with two goals: increasing public awareness of the problems of prematurity and reducing preterm delivery by 15%. This endeavor follows a 2002 survey of the public and a subset of pregnant women, which revealed that most people do not view prematurity as a serious problem and do not attribute associated complications with being born too early.^24,25

As part of the campaign, the March of Dimes will develop activities in the areas of public awareness, parent education, professional education, research, and advocacy. Support for these areas will in-clude mobilization of expert advisors, March of Dimes volunteers and staff, network and financial resources, sustained funding over several years, and development of an effective evaluation component. A Prematurity Campaign Scientific Advisory Committee has been established that includes representatives from ACOG, the American Academy of Pediatrics, and the Association of Women's Health, Obstetrical and Neonatal Nurses.

The aims of the Prematurity Campaign are to:

• Raise public awareness of the problems of prematurity.

• Invest more public and private research dollars to identify causes of preterm labor and prematurity, and to identify and test promising interventions.

• Educate pregnant women and their families to recognize the signs of preterm labor, support parents of babies in NICUs, and recognize the need for risk reduction.

• Assist health-care professionals in improving prematurity risk detection and addressing risk-associated factors.

• Expand access to health insurance in order to improve prenatal care and infant health outcomes.

The March of Dimes already has a well-known track record in the field of prematurity. Our involvement was noteworthy early on, with the 1976 landmark regionalization report to improve infant survival, "Toward Improving the Outcome of Pregnancy"—often referred to as TIOP I. This was followed in 1993 by an expanded and more comprehensive "Toward Improving the Outcome of Pregnancy: the 1990s and Beyond" (TIOP II), which stressed the recommendations from TIOP I and the importance of the continuum of reproductive health and preconceptional health. March of Dimes also has an important research portfolio related to prematurity and low birthweight, including support for research on regionalization, surfactant and nitric oxide therapies, the role of infections, enhanced prenatal care, substance abuse, and nutrition.

These efforts were expanded beginning in 1998 with the innovative Perinatal Epidemiological Research Initiative (PERI), which supports six grantees who are investigating social determinants and biological systems associated with preterm delivery. PERI is already yielding novel findings related to the pathogenesis of preterm labor as well as important genetic, nutritional, stress, psychosocial, and clinical factors (see "Prematurity: Born too soon, too small," http://www.marchofdimes.com/files/prematurity1.pdf and special supplement 2001 July Paediatric and Perinatal Epidemiology http://www.marchofdimes.com/printableArticles/681_4029.asp?printable=true ). These grants were recently renewed, extending the funding of this research to 2005.

In addition to the research focus, professional education will be a priority. As part of the Prematurity Campaign, there will also be a new collaborative grand rounds initiative with the Johnson and Johnson Pediatrics Institute. Interested physicians should contact their local March of Dimes chapter or Dr. Karla Damus at the National March of Dimes (kdamus@marchofdimes.com or 914-997-4463). The March of Dimes Web site ( www.marchofdimes.com ) also is being expanded and will include many professional educational tools, slide sets, and other materials to assist clinicians as they daily strive to improve perinatal health and prevent preterm delivery.

The March of Dimes commitment to this challenging 5-year national campaign affirms the importance of addressing the issue of prematurity. The campaign plan identifies opportunities for expanded national partnerships and points the way for increased state mission leadership. It outlines how the resources and energy of the foundation will be marshaled in support of advancing our mission and improving the health of babies. We are counting on our colleagues in obstetrics to join these efforts. Together we can help turn the pessimism to optimism in addressing this important obstetrical challenge.

REFERENCES

1. Bhutta AT, Cleves MA, Casey PH, et al. Cognitive and behavioral outcomes of school-aged children who were born preterm: a meta-analysis. JAMA. 2002;288:728-737.

2. Wood NS, Marlow N, Costeloe K, et al. Neurologic and developmental disability after extremely preterm birth. EPICure Study Group. N Engl J Med. 2000;343:378-384.

3. Lewit EM, Baker LS, Corman H, et al. The direct cost of low birth weight. Future Child. 1995;5:35-56.

4. National Center for Health Statistics. Natality Data 2000.

5. Romero R, Gomez R, Chaiworapongsa T, et al. The role of infection in preterm labour and delivery. Paediatr Perinat Epidemiol. 2001;15:41-56.

6. Cnattinguis S, Bergstrom R, Lipworth L, et al. Prepregnancy weight and the risk of adverse pregnancy outcomes. N Engl J Med. 1988;338:147-152.

7. Galtier-Dereure F, Montpeyroux F, Boulot P, et al. Weight excess before pregnancy: complications and cost. Int J Obes Relat Metab Disord. 1995;19:443-448.

8. Olsen P, Laara E, Rantakillio P, et al. Epidemiology of preterm delivery in two birth cohorts with an interval of 20 years. Am J Epidemiol. 1995;142:1184-1193.

9. Boer K, Smith BJ, van Huis AM, et al. Substance abuse in pregnancy: do we care? Acta Paediatr Suppl. 1994;404:65-71.

10. Slattery MM, Morrison JJ. Peterm delivery. Lancet. 2002;360:1489-1497.

11. Hogue CJ, Hoffman S, Hatch MC. Stress and preterm delivery: a conceptual framework. Paediatr Perinat Epidemiol. 2001;15:30-40.

12. Wadhwa PD, Culhane JF, Rauh V, et al. Stress, infection and preterm birth: a biobehavioural perspective. Paediatr Perinat Epidemiol. 2001;15:17-29.

13. Collaborative Group on Preterm Birth Prevention. Multicenter randomized controlled trial of a preterm birth prevention program. Am J Obstet Gynecol. 1993;169:352-366.

14. U.S. Public Health Service. Caring for Our Future: The Content of Prenatal Care. Washington, DC. NIH publication 90-3182.

15. Iams JD, Newman RB, Thom EA, et al. Frequency of uterine contractions and the risk of spontaneous preterm delivery. N Engl J Med. 2002;346:250-255.

16. Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academy Press. 2000:8-17.

17. March of Dimes Birth Defects Foundation. Is early prenatal care too late? Contemporary OB/GYN. 2002;47(December):54-72.

18. Goldenberg RL, Rouse DJ. Prevention of premature birth. N Engl J Med. 1998;339:313-320.

19. Findings from the 1992-98 Patient Outcomes Research Team on Low Birthweight. Clinical Highlight. AHRQ Publication No. 00-P010, January 2000. Agency for Healthcare Research and Quality, Rockville, MD. http://www.ahrq.gov/clinic/lobrhigh.htm .

20. Management of Preterm Labor. File Inventory, Evidence Report/Technology Assessment: Number 18. AHRQ Publication No. 01-E021, December 2000. Agency for Healthcare Research and Quality, Rockville, MD. http://www.ahrq.gov/clinic/prtrminv.htm .

21. ACOG Practice Bulletin. Assessment of risk factors for preterm birth. Clinical management guidelines for obstetrician-gynecologists. Number 31, October. 2001. Obstet Gynecol. 2001;98:709-716.

22. ACOG Practice Bulletin. Perinatal care at the threshold of viability. Clinical management guidelines for obstetrician-gynecologists. Number 38, September 2002. Obstet Gynecol. 2002;100:617-624.

23. Lockwood C. Predicting premature delivery—no easy task. N Engl J Med. 2002;346:282-284.

24. Massett HA, Greenup M, Ryan CE, et al. Public perceptions about prematurity: a national survey. Am J Prev Med. (In press) 2003.

25. Green NS, Ryan CE, Shusterman L, et al. Understanding pregnant women's perspectives on preterm birth. Contemporary OB/GYN. 2003;48(January):70-87.

 

Ellen Fiore. Taking action against prematurity. Contemporary Ob/Gyn 2003;2:92-104.