1. Late preterm infant: Is it a trend or a catastrophe? Michael E. Speer, MD Professor of Pediatrics & Medical Ethics Baylor College of Medicine

2. Survival of extremely low-birth-weight infants (birth weight < 1000 g) increased 35% between the 1980s and the 1990s Survival of extremely low-birth-weight infants (birth weight < 1000 g) increased 35% between the 1980s and the 1990s –85% of infants with very low birth weight (between 500 and 1500 grams) survive Stoelhorst GMSJ, et. al.Pediatrics. 2005 Feb;115(2):396-405. Stoelhorst GMSJ, et. al. Pediatrics. 2005 Feb;115(2):396-405. Improved Survival

3. Mortality: 1980s 1990s Mortality: 1980s 1990s –32 weeks’ gestation: 30% to 11% –<27 weeks’ gestation: 76% to 33% Stoelhorst GMSJ, et. al. Pediatrics. 2005 Feb;115(2):396-405.

4. Increased Morbidity Disabilities have also increased between 1980s & 1990s Disabilities have also increased between 1980s & 1990s –Primarily chronic lung disease and neuro-developmental impairment Sepsis: 37% to 51% Sepsis: 37% to 51% Periventricular leukomalacia: 2% to 7% Periventricular leukomalacia: 2% to 7% CLD: (O 2 at 36 wks PMA): 32% to 43% CLD: (O 2 at 36 wks PMA): 32% to 43% Cerebral palsy: 16% to 25% Cerebral palsy: 16% to 25% Deafness 3% to 7% Deafness 3% to 7% Neurodevelopment impairment* 26% to 36% Neurodevelopment impairment* 26% to 36% (*major neurosensory abnormality and/or Bayley Mental Developmental Index score of <70) Stoelhorst 2005. Pediatrics. 2005 Feb;115(2):396-405.

6. Rising Rate of Prematurity The preterm birth rate has increased by 36% since the 1980s* The preterm birth rate has increased by 36% since the 1980s* –> 540,000 each year at present –21% increase since 1990 (10.6% to 12.8%) Primarily 34 to 36 weeks gestation Primarily 34 to 36 weeks gestation –Increase of 25% since 1990 *NCHS 2006 final natality data; March of Dimes, 2009

7. Trends in Late Preterm Birth, Stillbirth, and Infant Mortality: US 1990-2004 Ananth CV, et al. Am J Obste Gynecol. 2008;199:329-31

8. Preterm Birth in the United States: 1996 - 2006 Preterm Birth in the United States: 1996 - 2006

9. Very Pre-Term Birth in the United States: 1996 - 2006

10. Late Preterm Births in the United States: 1996 - 2006

11. Source: National Center for Health Statistics Prepared by March of Dimes, Periantal Data Center, 2009 Percent of live births >70% Late Preterm Courtesy of Karla Damus RISE IN LATE PRETERM BIRTHS (34-36 wks) RISE IN LATE PRETERM BIRTHS (34-36 wks)

12. 37% 36 weeks 35 weeks 21% 13% 34 weeks <32 weeks 33 weeks7% 5% 32 weeks 16% Late preterm 71% DISTRIBUTION OF ALL US PRETERM BIRTHS 2004 www.marchofdimes.com Late Preterm Birth: Every Week Matters 03/06

13. Rising Rate of Prematurity Births by Gestational Age Births by Gestational Age http://www.cdc.gov/datastati stics/2007/births/

14. Distribution of Births, by Gestational Age -- United States, 1990 and 2005 http://www.cdc.gov/datastatistics/2007/births/

17. Percentage of Births by Cesarean: 32% (2007)

18. Births by caesarean section by country (2000) # 1 Italy:333 live births per 1,000 (33.3%)Italy # 2 Australia:217 live births per 1,000 (21.7%)Australia # 3 USA:211 live births per 1,000 (21.1%)USA # 4 Germany:209 live births per 1,000 (20.9%)Germany # 5 Canada:205 live births per 1,000 (20.5%)Canada # 6 Ireland:204 live births per 1,000 (20.4%)Ireland # 7 New Zealand:202 live births per 1,000 (20.2%)New Zealand # 8 Austria:172 live births per 1,000 (17.2%)Austria # 9 France:171 live births per 1,000 (17.1%)France # 10 United Kingdom:170 live births per 1,000 (17.0%)United Kingdom # 11 Belgium:159 live births per 1,000 (15.9%)Belgium # 12 Finland:157 live births per 1,000 (15.7%)Finland # 13 Denmark:145 live births per 1,000 (14.5%)Denmark # 14 Sweden:144 live births per 1,000 (14.4%)Sweden # 15 Norway:137 live births per 1,000 (13.7%)Norway # 16 Netherlands:129 live births per 1,000 (12.9%)Netherlands Weighted average:185.3 live births per 1,000 (18.5%)

19. Cesarean Section Rates – Latin America (2005) Median rate 33% (quartile range 24–43) Elective 49% Intrapartum 46% Emerg. s Labour5% Lancet. 2006;367:1819-29

20. World Wide Cesarean Section Rates - WHO Asia – 27.3% (2007 – 2008)* – –China 46.2% – –Sri Lanka30.6% – –Viet Nam35.6% – –Thailand 34.1% Latin America – 35% (2005) – –Brazil36% (2009) Private clinic rate: >90% – –Ecuador40% (2005) – –Paraguay42% (2005) *Lancet. 2010;375:Pages 490-499375:

21. Rates are not necessarily currenthttp://blog.fortiusone.com/2009/04/22/birth-in-the-usa/

23. Risks & Benefits of Elective Delivery  Risks in a Subsequent Pregnancy

24. Risk of Placenta Accreta and Hysterectomy by Number of Cesarean Deliveries Compared with the First Cesarean Delivery Cesarean Section Accreta [n(%)] Odds Ratio Hysterectomy [n(%]) Odds Ratio First 15 (0.2)  40 (0.7)  Second 49 (0.3) 1.3 (.7–2.3) 67 (0.4) 0.7 (0.4–0.97) Third 36 (0.6) 2.4 (1.3–4.3) 57 (0.9) 1.4 (0.9–1.2) Fourth 31 (2.1) 9.0 (4.8–16.7) 35 (2.4) 3.8 (2.4–6.0) Fifth 6 (2.3) 9.8 (3.8–25.5) 9 (3.5) 5.6 (2.7–11.6) Six or More 6 (6.7) 29.8 (11.3–78.7) 8 (9.0) 15.2 (6.9–33.5) Obstet Gynecol 2006;107:1226–32.

25. Indications for Late Preterm Birth % 23.2 Reddy U, et al. Pediatrics. 2009;124:234-9 14.4 15.9 1.3 48.9

26. Clinical Issues Risks of Elective Delivery –13,258 Elective Cesarean Sections Rates of adverse respiratory outcomes, mechanical ventilation, sepsis, hypoglycemia, NICU admission, and hospitalization for 5 days or more. Increased by a factor of 1.8 to 4.2 for births at 37 weeks Increased by a factor of 1.3 to 2.1 for births at 38 weeks. Tita A, et al. NEJM. 2009;360:111-120

27. Clinical Issues http://www.femalepatient.com/html/arc/sig/PatS/articles/034_09_041.asp

28. Khashu, M. et al. Pediatrics 2009;123:109-113 Mortality Higher in Preterm (33-36 wk) versus Term (37-40 wk)

29. Mortality: Late Preterm vs Term Infant: 1995-2002 Mortality/1000 live births Late PTTermRatio Overall (0 – 364 days) 7.92.43x Early neonatal (0 – 6 days) 2.80.56x Late neonatal (7 – 27 days) 1.40.43x Post neonatal (28-364 days) 3.71.62x Tomashak KM. J Pediatr 2007; 151;450

30. Khashu, M. et al. Pediatrics 2009;123:109-113 RR of morbidity, preterm versus term

31. Shapiro-Mendoza, C. K. et al. Pediatrics 2008;121:e223-e232 Proportion with newborn morbidity during birth hospitalization according to gestational age

32. Clinical outcomes in near-term and full-term infants (% of patients studied) Wang, M. L. et al. Pediatrics 2004;114:372-376

33. Early Respiratory Morbidity in Late Preterm Infants 3435363739 TTN (%) 2.41.61.10.70.4 Ventilator (%) 3.31.70.80.50.3 Weeks of Gestation McIntire & Leveno. Obstet. Gynecol. 2008;111:35-41

34. Early Respiratory Morbidity GA (wk)Oxygen > 1 hour Assisted Ventilation 38-40Reference 372.04 (1.61-2.59)2.35 (1.84-3.02) 364.95 (3.95-6.21)5.24 (4.11-6.68) 358.76 (6.77-11.4)0.04 (6.88-11.9) 3418.67 (14-24.9)19.8 (14.7-26.6) Odds Ratios Escobar GJ. Semin Perinatal. 2006;30:28-33

35. Early & Late Nutritional Morbidity Inadequate caloric intake: Inadequate caloric intake: –Poor suck/swallow coordination –Fatigue Feeding intolerance Feeding intolerance –Delayed stooling –Feeding residuals Exaggerated physiologic jaundice Exaggerated physiologic jaundice Dehydration Dehydration Hypernatremia Hypernatremia Increased need for parenteral nutrition Increased need for parenteral nutrition Failure to thrive Failure to thrive

36. Breastfeeding Issues Decreased milk production Decreased milk production Poor latch Poor latch Poor sucking effort Poor sucking effort Poor coordination Poor coordination Potential alteration in bonding Potential alteration in bonding

37. Wang, M. L. et al. Pediatrics 2004;114:372-376 Neonatal gestational age versus length of hospital stay

38. Primary Reason Documented for Discharge Delay of Near-Term and Full-Term Neonates Primary Reason for Delay of Discharge Near Term Full TermComment Jaundice8/49 (16.3%) 1/36 (0.03%) P =.072; 95% CI: 0.083–311.1; OR: 6.71 Respiratory distress8/26 (30.8%) 2/4 (50%) P =.58; 95% CI: 0.03–7.36; OR: 0.46 Poor feeding22/29 (75.9%) 2/7 (28.6%) P =.029; 95% CI: 0.94–93.4; OR: 7 Neonates (total) with discharge delay507 Wang, M. L. et al. Pediatrics 2004;114:372-376

39. GA at Presentation to ED: 2003 Jain S. Clinics in Perinatology. 2006;33:935-945Clinics in Perinatology

40. Age at presentation to ED Jain S. Clinics in Perinatology. 2006;33:935-945Clinics in Perinatology

41. Lung Maturation Pulmonary Pulmonary –Persistent airway obstruction demonstrated in healthy premature infants (  36 wk GA) compared with infants born at term: 6–10 weeks after birth:  FEF in healthy 30–34 wk GA infants (P<0.001) 1 6–10 weeks after birth:  FEF in healthy 30–34 wk GA infants (P<0.001) 1 At age 1:  V max FRC in healthy 29–36 wk GA infants (P<0.05) 2 At age 1:  V max FRC in healthy 29–36 wk GA infants (P<0.05) 2 1.Friedrich L, et al. 1.Friedrich L, et al. Am J Resp Crit Care Med. 2006;173:442-447. 2 2.Hoo A-F, et al. J Pediatr. 2002;141:652-658. FEF: forced expiratory flow; V max FRC: maximal expiratory flow at functional residual capacity.

42. Boyce TG, et al. J Pediatr. 2000;137:865-870.  28 wks GA Low-risk**29 to <33 wks GA 33 to <36 wks GA RSV-related Hospitalizations per 100 Children <6 Months of Age BPDCHD *Retrospective study of enrollees in Tennessee Medicaid, July 1989-June 1993. **Low-risk defined as all other children born at term. Risk of Infection: RSV 56.3 12.1 9.48.28.04.4 Infection

43. Changes in brain volume and maturation with increasing gestational age Kapelloou, O et al. PLOS Med 2006;3:e265

44. Brain Growth During Gestation Hüppi PS, et al. Ann Neurol. 1998 Feb;43(2):224-35.

45. Neuronal Maturation 31 wk post conceptual age 40 wk post conceptual age Hüppi PS, et al. Ann Neurol. 1998 Feb;43(2):224-35.

46. Neurologic Maturation: Cerebral White Matter Hüppi PS, et al. Ann Neurol. 1998 Feb;43(2):224-35.

47. Neurologic Maturation From Conel, 1939-59

48. Neurodevelopmental Early School-Age Outcome Age% Late Preterm Late PretermN=7152 % Term N=152, 661 Unadjusted RR [95% CI] Adjusted RR [95% CI] Developmental delay/disability 0–34.242.961.43 (1.36–1.51)1.36 (1.29–1.43) Disability in prekindergarten34.463.891.15 (1.09–1.20)1.13 (1.08–1.19) Disability in prekindergarten47.406.601.12 (1.08–1.16)1.10 (1.05–1.14) Not ready to start school45.094.401.16 (1.11–1.21)1.04 (1.00–1.09) Exceptional student education 513.3011.91.13 (1.09–1.16)1.10 (1.07–1.13) Retention in kindergarten57.966.171.29 (1.24–1.34)1.11 (1.07–1.15) Suspension in kindergarten51.801.221.48 (1.37–1.60)1.19 (1.10–1.29) Morse SB et al. Pediatrics. 2009;123:e622-e629

49. Morse, SB et al. Pediatrics 2009;123:e622-e629 Percentage of children with adverse early school-age outcome by gestational age

50. Disabilities Related to GA at Birth (Adults) % *RR: 2.7(2.2 – 3.3) +RR: 1.6(1.4 – 1.8) ^RR: 1.4(1.3 – 1.5) #RR: 1.5(1.2 – 1.8) * Cerebral Palsy + Mental Retardation ^ Disability Affecting Work # Other Major Disability Moster D et al. NEJM. 2008; 359:262-273