1. The National Prematurity Campaign: A Call to Action Karla Damus RN MSPH PhD Dept OB/GYN and Women’s Health Albert Einstein College of Medicine, Bronx, NY Office of the Medical Director National March of Dimes, White Plains, NY kdamus@marchofdimes.com 914 997 4463

3. March of Dimes National Prematurity Campaign 2003-2007 5 year $75 million initiative

4. National Professional Partners ACOG AAP AWHONN Many national professional health group alliances

5. Campaign Goals 1. Increase public awareness of the problems of prematurity to at least 60% 2. Decrease the rate of preterm birth in the U.S. by at least 15%

6. March of Dimes Prematurity Campaign 2003-2007 5 Campaign Aims: 1. Raise public awareness 2. Educate women as to signs of premature labor 3. Assist practitioners 4. Invest to identify causes and promising interventions 5. Seek guaranteed access to health care

7. www.cdc.gov/brfss

8. Preterm Birth/Prematurity Single most important cause of perinatal mortality (28 weeks gestation through 6 days of life) in US (about 75% of these losses) Leading cause of neonatal mortality (0-27 days) in US Second leading cause of infant mortality in US Leading cause of infant mortality in GA and leading cause of infant mortality for black infants in the US Major determinant of neonatal and infant illness: –Neurodevelopmental handicaps (CP, mental retardation) –Chronic respiratory problems –Intraventricular hemorrhage –Periventricular leukomalacia –Infection –Retrolental fibroplasia –Necrotizing enterocolitis –Neurosensory deficits (hearing, visual)

9. Prematurity Generates Enormous Health Care Costs Average newborn hospital charges: $4,300 vs. $58,000 for a preterm baby* Total U.S. hospital charges for infant stays due to prematurity/low birth weight: $11.9 Billion* Maternity & related expenses: –Often the largest cost to employers’ health care plans * Source: Agency for Healthcare Research and Quality, 2000 Nationwide Inpatient Sample Prepared by March of Dimes Perinatal Data Center, 2003

10. March of Dimes Birth Defects Foundation Mission: To improve infant health by preventing infant mortality and birth defects The Continuum of Reproductive Health Improving health of infants requires focusing on the entire spectrum of reproductive health which extends from prior to conception through the first year of an infant’s life and throughout the woman’s childbearing years Preconceptional health is the cornerstone of healthy infants, children, families and communities

11. Conception Birth 1 Year Fetal Infancy 20 wks28 wks4 wks Spontaneous Abortion Early Fetal Late Fetal Neonatal Postneonatal Infant Feto-Infant Perinatal I II III Age at Loss Ectopic

12. Critical Periods of Development 4 5 6 7 8 9 10 11 12 Weeks gestation from LMP Central Nervous System Heart Arms Eyes Legs Teeth Palate External genitalia Ear Missed Period Mean Entry into Prenatal Care Most susceptible time for major malformation

13. Unintended Pregnancies United States, 1994 Percent Source: National Survey of Family Growth, 1995 Prepared by March of Dimes Perinatal Data Center, 2000

14. www.marchofdimes.com or peristats.modimes.org

15. www.health.state.ok.us

16. Percent of Births by Race/Ethnicity Oklahoma and US 1999-2001 Average

17. Infant Mortality United States, 1915-2000 Rate per 1,000 live births Source: National Center for Health Statistics, final mortality data Prepared by March of Dimes Perinatal Data Center, 2002

18. Infant Mortality Rates Oklahoma and US, 1990-2000 OK IMR decrease 31.4% US IMR decrease 25.0%

19. Annual Black/White Infant Mortality Rate Ratio United States, 1980-2000 Source: NCHS, final mortality data Alexander G., SACIM, 2001.

20. 1995-97 Birth Weight-Specific Infant Mortality Rates by Race Source: NCHS, final mortality data Alexander G., SACIM, 2001.

21. Selected Leading Causes of Infant Mortality United States, 1990 and 2000 Rate per 100,000 live births Source: National Center for Health Statistics, 1990 final mortality data and 2000 linked birth/infant death data Prepared by March of Dimes Perinatal Data Center, 2002 1 2 3 6 2000 Rank

22. Leading Causes of Infant Mortality Oklahoma and US, 2000

23. State Rankings : 43 32 41 IMR, PTB, and Adequate/+ PNC US and OK, 1998-2000 avg and HP2010

24. Low Birthweight Births 7.8% Preterm Births 12.0% Birth Defects ~3-4% Overlap in LBW, Preterm and Birth Defects U.S. (2002) Among LBW: 2/3 are preterm Among preterm: almost 50% are LBW (some preterm are not LBW)

25. Preterm Births United States, 1981, 1991, 2001, 2002 Source: National Center for Health Statistics, final natality data Prepared by March of Dimes Perinatal Data Center, 2003 Percent Healthy People Objective March of Dimes Objective 27 Percent Increase 1981-2001

26. Preterm Births (<37 weeks) by Maternal Race/Ethnicity, US, 2001 Percent Preterm is less than 37 weeks gestation Hispanics can be of any race Source: National Center for Health Statistics, 2000 final natality data Prepared by March of Dimes Perinatal Data Center, 2002

27. Preterm Delivery (<37 wks) Oklahoma and US, 1991-2001 OK PTB increase 0.8% US PTB increase 10.2%

28. Singleton Preterm Births by Race/Ethnicity United States, 1990 and 2000 Percent Source: National Center for Health Statistics, 1999 final natality data Prepared by March of Dimes Perinatal Data Center, 2002

29. Very Preterm (<32 wks) by Maternal Age Oklahoma and US, 1999-2001 average

30. Types of Preterm Birth Spontaneous Preterm Labor Spontaneous Premature Rupture of the Membranes Medical Intervention Preterm Birth While this suggests distinct pathways, many of the risk factors for all 3 are similar

31. Risk Factors for Preterm Labor/Delivery The best predictors of having a preterm birth are: current multifetal pregnancy a history of preterm labor/delivery or prior low birthweight mid trimester bleeding (repeat) some uterine, cervical and placental abnormalities Other risk factors: –multifetal pregnancy –maternal age ( 35 yrs) –black race –low SES –unmarried –previous fetal or neonatal death –3+ spontaneous terminations –uterine abnormalities –incompetent cervix –genetic predisposition –low pre-pregnant weight –obesity –infections –bleeding –anemia –major stress –lack of social supports –tobacco use –illicit drug use –alcohol abuse –folic acid deficiency

32. Folic Acid Deficiency Predisposes to: NTDs Other birth defects (cleft lip/palate, cardiac, limb reduction, urinary tract, omphalocele, trisomies) Early and recurrent pregnancy loss Low birth weight and prematurity ?Gestational hypertension Atherosclerotic vascular disease (stroke, CAD) Colorectal and cervical cancer Acute Lymphocytic Leukemia Alzheimer’s Disease

33. Folic Acid Recommendations Prevent Recurrence, 1991 All women with a previous NTD pregnancy should take 4 mg or 4000mcg interconceptionally Prevent Occurrence, USPHS September, 1992 All women of childbearing potential should consume 0.4 mg (400 micrograms) of folic acid daily Food & Nutrition Board of IOM, 1998 Men (14 yr & older) 400 µg any source Women (14 yr & older) 400 µg synthetic + food Pregnancy 600 µg synthetic + food Lactation 500 µg any source

34. www.cdc.gov/brfss

35. Folic Acid Knowledge and Behavior 1995 and 2003 Percentage of women ages 18-45

36. Reasons Why Women Do Not Take a Multivitamin Daily March of Dimes Folic Acid Survey, 2003

37. Things Women Reported Might Encourage them to Take a Multivitamin Daily March of Dimes Folic Acid Survey, 2003

38. Factors that Contribute to Increasing Rates of Preterm Birth Increasing rates of births to women 35+ years of age Increasing rates of multiple births Indicated deliveries –Epidurals –Induction (What happened to labor support?) –Enhanced management of maternal and fetal conditions –Patient preference/consumerism Substance abuse –Tobacco –Alcohol –Illicit drugs Bacterial and viral infections Increased stress (catastrophic events, DV, racism)

39. Percent of Births by Maternal Age Oklahoma and US 1999-2001 Average

40. Multiple Birth Ratios Oklahoma and US, 1996-2001

41. Multiple Birth Ratios by Race* United States, 1980-2001 Ratio per 1,000 live births *Race of child from 1980-1988; Race of mother from 1989-2001 Source: NCHS, final natality data, 1980-2001 Prepared by March of Dimes Perinatal Data Center, 2003

42. Multiple Birth Ratios by Maternal Age Oklahoma and US, 1999-2001 average

43. Higher Order Birth Ratios by Race* United States, 1980-2001 Ratio per 100,000 live births *Race of child from 1980-1988; Race of mother from 1989-2001 Source: NCHS, final natality data, 1980-2001 Prepared by March of Dimes Perinatal Data Center, February 2003

44. Risks of Adverse Pediatric Outcomes with ART Multiples Twins - 20-40% Triplets - 0.5-9.3% Prematurity Low birth weight Birth Defects? Complicated analysis Maternal: Low birth weight, Birth defects Paternal: Chromosomal abnormalities Procedures: ICSI - Imprinting defects ?

45. Singletons Preterm Delivery Oklahoma and US, 1991-2001

46. Total and Primary Cesarean and VBAC Rates, United States, 1989-2001

47. All Delivery Methods Categories Oklahoma and US, 2001

48. Singleton Preterm Births by Delivery Method United States, 1990 and 2000 Percent

49. All Substance Use Categories Oklahoma and US, 2001

50. Impact of Smoking Smoking during pregnancy is responsible for: –20% of all LBW –8% of preterm births –5% of all perinatal deaths Pregnant smokers compared to nonsmokers are: –2.0-5.0 times as likely to experience PPROM –1.2-2.0 times as likely to deliver preterm –1.5-10 times as likely to deliver a SGA infant –1.5-3.5 times as likely to deliver a LBW infant Smoking increases risk of stillbirth (RR=1.4-1.6) –Risk increases with increased amount smoked Smoking during and after pregnancy increases risk for SIDS by 3-fold

51. The 5 A’s 1. Ask about tobacco use 2. Advise to quit 3. Assess willingness to make a quit attempt 4. Assist in quit attempt 5. Arrange follow-up A Clinician’s Guide to Helping Pregnant Women Quit Smoking

52. www.cdc.gov/brfss

55. Effects of Alcohol on Pregnancy Miscarriage Premature birth Low birth weight FAS ARBD - Alcohol-Related Birth Defects ARND - Alcohol-Related Neurodevelopmental Disorders Birth complications

56. www.cdc.gov/brfss

61. Can Preterm Labor be Prevented? Primary prevention is the goal –especially risk reduction in the preconceptional period and early in pregnancy Preterm prevention programs have focused on risk assessment or prediction of preterm labor –risk assessment identifies only half of preterm births –during pregnancy most biomarkers, even in combination with risk factors, do not have good positive predictive values Causation is the great unknown

62. What interventions may work? “Most efforts to prevent preterm labor have not proven to be effective, and equally frustrating, most efforts at arresting preterm labor once started have failed”. “The most important components of management, therefore, are aimed at preventing neonatal complications through the use of corticosteroids, and antibiotics to prevent GBS and avoiding traumatic deliveries.” Goldenberg RL. The management of preterm labor. Obstet Gynecol 100 (5):1020- 36, 2002.

63. Evidence Based Guidelines Management of Preterm Labor, Evidence Report /Technology Assessment, No 18, AHRQ, 2000 (www.ahrq.gov) Assessment of Risk Factors for Preterm Birth, ACOG Practice Bulletin, No 31, October 2001 (www.acog.gov) Perinatal Care at the Threshold of Viability, ACOG Practice Bulletin, No 38, September 2002 Criteria for Determining Disability in Infants and Children: Low Birth Weight, Evidence Report/Technology Assessment No 70, AHRQ, 2003 VBAC, Evidence Report/Technology Assessment, No 71, AHRQ, 2003 Management of Preterm Labor, ACOG Practice Bulletin, No 43, May 2003 Use of Progesterone to Reduce Preterm Birth ACOG Committee Opinion, No 291, November 2003

64. Management of Preterm Labor ACOG Practice Bulletin, No 43, May 2003 Level A (good and consistent scientific evidence) –There are no clear “first line” tocolytic drugs to manage PTL. Clinical circumstances and physician preferences should dictate treatment –Abs do not appear to prolong gestation and should be reserved for GBS prophylaxis in patients in whom delivery is imminent –Neither maintenance treatment with tocolytic drugs nor repeated acute tocolysis improve perinatal outcome; neither should be undertaken as a general practice –Tocolytics may prolong pregnancy for 2-7 days, which may allow for administration of steroids to improve fetal lung maturity and the consideration of maternal transport to a tertiary care facility

65. Management of Preterm Labor ACOG Practice Bulletin, No 43, May 2003 Level B (limited or inconsistent scientific evidence) –Cervical ultrasound exam and fFN testing have good negative predictive value; thus, either approach or both combined may be helpful in determining which patient do not need tocolysis –Amniocentesis may be used in women in PRL to assess fetal lung maturity and intraamniotic infection –Bed rest, hydration and pelvic rest do not appear to improve the rate of preterm birth and should not be routinely recommended.

66. Recent Developments in Obstetrics Preelampsia –5-11% of pregnancies (3% in England), 15% of pregnancy-related deaths, 25% of VLBW –uterine artery Doppler ultrasound can identify women at risk –prophylactic low dose aspirin will reduce risk of preeclampsia and fetal death by 15% –Antioxidants (vitamin C and E) promising Second trimester use of ultrasound to measure cervical length and the detection of vaginal fFn are better predictors of preterm birth than previous history There is no evidence that asymptomatic women with abnormal vaginal flora benefit from antimicrobials Shennan HS. BMJ 327:604-608, 2003.

67. Recent Developments in Obstetrics Evidence regarding prophylactic abs use is contradictory since benefit may be related to the choice, route and timing of treatments External cephalic version should be offered to women with term breech presentation (3% increased risk of death or serious morbidity to their baby with breech delivery) Intrapartum interventions can be reduced by avoiding unnecessary electronic fetal monitoring, encouraging vaginal delivery with previous cesarean section and using low dose epidurals. ?fish oils- prospective trials needed The biggest impact to prevent prematurity is probably simple: avoid smoking Shennan HS. BMJ 327:604-608, 2003.

68. March of Dimes Investment in the Science and Public Health of Preterm Delivery Toward Improving the Outcome of Pregnancy (TIOP I)- regionalization of perinatal care TIOP II - regionalization, continuum, elimination of health disparities >$15 Million for research since 1985, 200 grants Innovative community intervention trials (late-80’s) Pittsburgh health community, contemporary intervention (P4 Project) Six innovative epidemiology research initiatives to define biomarkers and mechanisms (1998-2004) –Perinatal Epidemiological Research Initiative (PERI)

69. March of Dimes PERI Perinatal Epidemiological Research Initiative 1998-2004 Epidemiologic approaches to test biologically plausible hypotheses for the major determinants of preterm birth Examine the interactions of risk factors associated with prematurity and relevant biologic samples

70. Pathways to Preterm Labor/Delivery Infection (ascending), 40% –cytokines Stress (maternal/fetal), 25% –CRH Bleeding (decidual hemorrhage, abruption), 25% –thrombin Stretching (uterine distention), 10%

71. proteases PTD Uterine Contractions Cervical change Infection: - Chorion-Decidual - Systemic Decidual Hemorrhage Abruption CRH E1-E3 Thrombin Thrombin Rc Pathological Uterine Distention Multifetal Preg Polyhydram Uterine abnorm Inflammation Maternal-Fetal Stress Premature Onset of Physiologic Initiators Activation of Maternal/Fetal HPA Axis CRH + + Chorion Decidua uterotonins Mechanical stretch Gap jct Oxt recep PG synthase PROM Ils, Fas L TNF Lockwood CL. Unpublished data. 2002.

72. Prevention of Preterm Labor, Preterm Delivery and Prematurity Primary prevention –identifying and managing risks –risk reduction approach and strategies to reproductive health –prevent PTL Secondary prevention –prevent preterm delivery Tertiary prevention –prevent/minimize complications of prematurity

73. Innovative Perspectives “The prevention of preterm delivery will require intervention at an earlier stage in the processes that lead to it.” Strategies are needed to prevent infections Therapies should be rigorously evaluated in women who have recurrent PTD due to disturbances in uterine blood vessels and blood flow Refine assisted reproductive techniques (ART) to reduce the occurrence of twin and higher-order multifetal pregnancies Lockwood CJ. Predicting premature delivery--No easy task. NEJM, 2002, 346 (4):282-4.

74. Interventions that Work Early, comprehensive, accessible prenatal care Educate all pregnant women about preterm labor signs and symptoms Screen and treat all UTIs and STIs Identify cigarette smokers and intervene (5As) Assess for alcohol use and intervene Identify illicit substance users and intervene Assess for domestic violence and intervene Eliminate folic acid deficiency Reduce major stress levels early and throughout pregnancy

75. Interventions that Work Provide culturally sensitive, age appropriate preconceptional care (risk reduction focus) - www.marchofdimes.com preconceptional curriculum for ob/gyns, pediatricians, internists, family practitioners www.marchofdimes.com Promote optimal weight Exercise and activity Good mental health Manage all chronic conditions (hypertension, diabetes) Oral health and periodontal disease ?Omega 3 fatty acid

76. www.cdc.gov/brfss

77. Progesterone study (high risk by history) –Multisite US, Meis, et, al MFMU-NICHD (preliminary)  by ~ 30% –da Fonesca (preliminary)  by 50%+ Clotting abnormalities (Thrombophilia) - Yale Genetic Can screen Can treat Stress research - CDC, MOD (PERI), Others Promising Research Directions

78. Take Home Message All pregnant women are at risk for preterm labor and birth Intervene throughout the continuum of reproductive health for women and men Everyone can make a difference

79. March of Dimes www.marchofdimes.com askus@marchofdimes.com

80. Premature Birth: The answers can’t come soon enough

81. Thank you for your attention Additional Resources www.marchofdimes.com www.jjpi.com this continuing education presentation is sponsored by the March of Dimes - Johnson & Johnson Pediatric Institute Grand Rounds Program as part of the M arch of Dimes National Prematurity Campaign