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Almost But Not Quite Term: Special Risks for Late Preterm and Early Term Infants

Almost But Not Quite Term: Special Risks for Late Preterm and Early Term Infants. Sarah N. Taylor, M.D. Assistant Professor, Division of Neonatology Medical University of South Carolina February 4, 2012. What is a “Late Preterm Infant”?. Near-term does not

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Almost But Not Quite Term: Special Risks for Late Preterm and Early Term Infants

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  1. Almost But Not Quite Term: Special Risks for Late Preterm and Early Term Infants Sarah N. Taylor, M.D. Assistant Professor, Division of Neonatology Medical University of South Carolina February 4, 2012

  2. What is a “Late Preterm Infant”? • Near-term does not • “capture how immature and vulnerable” Moderately preterm Near term Minimally preterm Marginally preterm Late Preterm NICHD workshop July 2005

  3. Late Preterm Infant Definition • NICHD: 34 0/7 to 36 6/7 weeks gestation • 34th week chosen secondary to obstetrical decision to not give antenatal steroids at that gestation • Other possibility: gestational age associated with “normal” birth weight (≥ 2500g) and can be admitted to normal newborn nursery (≥ 35 weeks) • 35 0/7 to 36 6/7 weeks gestation 37 0/7 - 37 6/7 weeks can also be “immature and vulnerable” Escobar GJ et al Semin Perinatol 2006; Ramachandrappa A & Jain L et al Pediatr Clin North Am 2009; Raju TN et al Pediatr 2006

  4. ACOG Has An Opinion • Fetal pulmonary maturity should be confirmed before scheduled delivery at less than 39 weeks of gestation unless fetal maturity can be inferred from historic criteria (criteria suggesting 39 weeks of gestation) ACOG Practice Bulletin No. 97 2008

  5. New Definition: Early-Term Birth • 37 0/7 to 38 6/7 weeks • Based on ACOG guidelines to delay elective deliveries to 39 0/7 • Supported by The March of Dimes, NICHD, Society for Maternal-Fetal Medicine Gyamfi-Bannerman C Semin Perinatol 2011; Clark SL et al Am J Obstet Gynecol 2009; Tita AT et al N Engl J Med 2009; Ashton DM Curr Opin Obstet Gynecol 2010; Spong CY et al Obstet & Gynecol 2011

  6. How Many Late Preterm Infants Are There? • 34-36 weeks gestation • 75% of preterm infants in U.S. • 35-36 weeks gestation • 7% of all live births in U.S. • 58.3% of preterm births in U.S. • Increasing population since 1990 • <34 weeks, by 10% • 34-36 weeks, by 25% Ramachandrappa A & Jain L Pediatr Clin North Am 2009; Sharpiro-Mendoza CK et al Pediatr 2008; Escobar GJ et al Semin Perinatol 2006

  7. How Many Early Term Infants Born By Elective Repeat C/section? • 24,077 at 19 centers 1999-2002 • 13,258 elective • 35.8% before 39 completed weeks • 6.3% at 37 weeks • 29.5% at 38 weeks • 49.1% at 39 weeks • Increased respiratory disease, mechanical ventilation, newborn sepsis, hypoglycemia, admission to NICU, and hospital stay >5 days • 37 weeks, adjusted odds 1.8-4.2 • 38 weeks, adjusted odds 1.3-2.1 Tita AT NEJM 2009

  8. Despite the size and growth of this population,minimal evidence-based practice and/or research available

  9. Despite the size and growth of this population,minimal evidence-based practice and/or research available Therefore, this group is scary for both neonatologists and pediatricians

  10. So, Why So Many Late Preterm Infants? • Delivery at 34 weeks considered “safe” • Cut-off for antenatal steroids • Increased fertility/multiples • Increased mothers with medical conditions • Pregnancy and non-pregnancy-related • Increased fetal monitoring • Babies are bigger Verklan MT Crit Care Nurs Clin North Am 2009; Davidoff MJ et al Semin Perinatol 2006; Raju TN Clin Perinatol 2006 Ramachandrappa A & Jain L Pediatr Clin North Am 2009; Shapiro-Mendoza CK et al Pediatr 2008; Escobar GJ et al Semin Perinatol 2006

  11. So, Why So Many Late Preterm Infants? • Delivery at 34 weeks considered “safe” • Cut-off for antenatal steroids • Increased fertility/multiples • Increased mothers with medical conditions • Pregnancy and non-pregnancy-related • Increased fetal monitoring • Babies are bigger • “I want this baby out” Verklan MT Crit Care Nurs Clin North Am 2009; Davidoff MJ et al Semin Perinatol 2006; Raju TN Clin Perinatol 2006 Ramachandrappa A & Jain L Pediatr Clin North Am 2009; Shapiro-Mendoza CK et al Pediatr 2008; Escobar GJ et al Semin Perinatol 2006

  12. Higher Induction and Cesarean Section Rates • Nearly 1 in 4 births born by induction • One in 3 births by cesarean section • Repeat c/section in 92% of women with primary c/section • Increases in inductions and c/sections are predominately in the late preterm and early term (34-39 weeks) • Most frequent length of a singleton pregnancy is now 39 weeks instead of 40 weeks gestation • Mean age of twin delivery: 35.3 weeks Verklan MT Crit Care Nurs Clin North Am 2009; Lee YM et al Clin Perinatol 2006; Ramachandrappa A & Jain L Pediatr Clin North Am 2009; CDC 2005

  13. Intermountain Healthcare System Had a Problem • 9 hospitals involved in process improvement • Pre-test: 28% of elective deliveries were <39 weeks • Intervention: presentation of the morbidities associated with delivery at <39 weeks • Rate of NICU admissions for normal pregnancies • 37 weeks: 8.9% • 38 weeks: 4.5% • 39 weeks: 3.3% • Rate of ventilator use for uncomplicated deliveries • 37 weeks: 1.4% • 38 weeks: 0.5% • 39 weeks: 0.3% Oshiro BT, Henry E et al. Obstet & Gyn 2009

  14. Results of Intervention Oshiro BT, Henry E et al. Obstet & Gyn 2009

  15. NICHD and Society for Maternal-Fetal Medicine Workshop 2/2011 • Timing of Indicated Late Preterm and Early Term Births From Spong CY, Mercer BM, D’Alton M et al. Timing of indicated late-preterm and early-term birth. Obstetr and Gynecol 2011;118:323-33.

  16. Definition of Indicated Late Preterm • Multiple reasons • Indicated: Preterm labor, rupture of membranes, pre-eclampsia, intrauterine growth restriction with abnormal testing, acute abruption, • Debatable Indication: IUGR with reassuring testing, gestational hypertenstion, mild pre-eclampsia, oligohydramnios Gyamfi-Bannerman C Semin Perinatol 2011; Zhang J et al Br J Obstet Gynaecol 2004; Holland MG et al Am J Ostet Gynecol 2009

  17. Indicated Late Preterm Delivery • Placenta previa, accreta, increta, percreta • Prior classical cesarean • IUGR with abnormal studies • Twins: mono-mono, mono-di, fetal death, IUGR • Oligohydramnios • Chronic hypertension with difficult control • Severe preeclampsia • Diabetes- poorly controlled • Rupture of membranes • Progressive labor Spong CY et al Obstetr & Gynecol 2011

  18. Indicated Early Term Delivery • Prior myomectomy necessitating cesarean • Singleton IUGR • Twins: di-di • Chronic hypertension-controlled • Mild preeclampsia • Diabetes- pregestational with vascular disease Spong CY et al Obstetr & Gynecol 2011

  19. If Delivering Late Preterm • Lung Maturity Testing • Lung profile does not represent other organs • If delivery is necessary, then deliver despite maturity • Antenatal Steroids • Recommended for preterm birth before 34 weeks • 1 RCT studied with elective C/section <39 weeks • Less neonatal respiratory distress admissions • However, delaying delivery to 39 weeks was associated with even less neonatal respiratory distress admissions Spong CY et al Obstetr & Gynecol 2011; Stutchfield P et al BMJ 2005

  20. What are the risks of late preterm delivery?

  21. Results of Early Delivery • Birth hospitalization • Median length of stay similar for “near-term” (35-36 weeks) and full-term • However, wide variations in hospital stay for near-term infants after both vaginal and cesarean deliveries Wang ML & Dorer DJ Pediatr 2004

  22. Hospitalization Following Elective Deliveries • Elective delivery with no medical indication • Admission to special care nursery • 17.8% at 37-38 weeks • 8% at 38-39 weeks • 4.6% ≥ 39 weeks • Mean length of stay 4.5 days Clark SL et al Am J Obstet Gynecol 2008

  23. Rehospitalization • Rates • 6.3% for 35-37 weeks; 3.4% for 38-40 weeks; 2.4% for >40 weeks (Oddie SJ et al Arch Dis Child 2005) • 4.3% late preterm; 2.7% term (Tomashek KM et al Semin Perinatol 2006) • Late rehospitalization (15-182 days post-discharge) • 9.1% for 34 wks; 6.8% for 35 wks; 7.3% of 36 wks; 5.6% for 37 wks, 4.4% for 38-40 wks, 3.6% for ≥40 wks (Escobar GJ et al Semin Perinatol 2006)

  24. Why Are Infants Rehospitalized? • Most common reasons • Jaundice, feeding difficulties, and/or dehydration • Predictors of rehospitalization CI- confidence interval Escobar GJ et al Semin Perinatol 2006; Oddie SJ et al Arch Dis Child 2005

  25. Risk Factors for Rehospitalization • Late preterm infants • 1.5 times more likely to require hospital-related care • 1.8 times more likely to be admitted Significant difference between breastfed late preterm and term infants No significant difference between not breastfed late preterm and term infants Tomashek KM et al Semin Perinatol 2006

  26. Mortality Risk • 2002 U.S. Mortality rate by gestational age • For 34-36 weeks, mortality rate of 7.9% which is 3 times higher than the term infant rate Escobar GJ et al Semin Perinatol 2006 Tomashek KM et al Semin Perinatol 2006; Tomashek KM et al J Pediatr 2007; Mathews TJ et al Natl Vital Stat Rep 2007

  27. Mortality Risk for Early Term? • Relative Risk of Mortality • At 37 weeks, 2.6-2.9 times the risk at 39 weeks • Also increased at 38 weeks compared to 39 weeks Reddy UM et al Obsetrics Gynecol 2011

  28. Neurodevelopment of the Late Preterm Infant • Brain growth compare to 40 weeks gestation • Cerebral volume is only 53% • Weight is 66% • Cerebral cortex has less gyri/sulci and is smooth • Myelination and interneuronal connectivity is incomplete Kinney HC Semin Perinatol 2006; Ramachandrappa A & Jain L Pediatr Clin North Am 2009; Adams-Chapman I Clin Perinatol 2006; Verklan MT Crit Care Nurs Clin North Am 2009

  29. Neurodevelopment Studies • 20-year follow-up of late preterm infants with no congenital anomalies • Higher incidence of • Cerebral palsy: Relative risk (RR) 2.7 • Mental retardation: RR 1.6 • Significantly increased psychological development problems, behavioral and emotional disturbances, and other major disabilities • More likely to receive disability allowance • Less likely to attain post-secondary degree Lindstorm; Moster D et al NEJM 2008

  30. In the United States • Late preterm compared to term births through kindergarten • 36% higher risk for developmental delay or disability • 19% higher risk for suspension in kindergarten • Repeat study controlling for neonatal complications • 35-36 week infants with admission to NICU had lower neurocognitive scores • Late preterm without complications were similar to term counterparts Morse SB et al Pediatr 2009; Baron IS Early Hum Dev 2011

  31. Early Years • Within first 3 years, compared to term infants • Increased diagnosis of developmental delay • Increased referrals for special needs preschool resources • Increased difficulties with school readiness Inder TE et al Ann Neurol 1999; Verklan MT Crit Care Nurs Clin North Am 2009

  32. So, experts are worried… • NICHD and Association of Women’s Health, Obstetric, and Neonatal Nurses • Research agenda to better understand short- and long-term medical complications that are associated with late preterm births • Anticipation and management of potential morbidities • Assistance with non-emergent obstetric intervention decisions

  33. We need further evidence for late preterm infant management and further medical support to extend pregnancies Why do we do in the meantime?

  34. Short-term Late Preterm Problems • Feeding Difficulties • Dehydration • Breastfeeding difficulties • Hypoglycemia • Hyperbilirubinemia • Temperature Instability • Increased sepsis work-ups • Respiratory Failure • RDS • TTN

  35. What is the Morbidity Risk? • Newborn morbidity risk • Late preterm infant- 22% • Term infant-3% Late preterm infants were 7 times more likely • Risk increases with decreasing gestational age • 38-41 wks: 3% 37 wks: 6% 34 wks: 52% • Compared to 40 weeks • 35 week infants had 10X’s the risk • 36 week infants had 5X’s the risk Shapiro-Mendoza CK et al Pediatr 2008

  36. How Many Early Term Infants Born By Elective Repeat C/section? • 24,077 at 19 centers 1999-2002 • 13,258 elective • 35.8% before 39 completed weeks • 6.3% at 37 weeks • 29.5% at 38 weeks • 49.1% at 39 weeks • Increased respiratory disease, mechanical ventilation, newborn sepsis, hypoglycemia, admission to NICU, and hospital stay >5 days • 37 weeks, adjusted odds 1.8-4.2 • 38 weeks, adjusted odds 1.3-2.1 Tita AT NEJM 2009

  37. Outcomes After Lung Maturity Testing • 36-38 6/7 weeks vs. 39-40 6/7 weeks • 6.1 vs. 2.5% for composite adverse neo outcome • Adjusted odds ratio • RDS 7.6 (Confidence interval 2.2-26.6) • Treated hyperbilirubinemia 11.2 (CI 3.6-34) • Hypoglycemia 5.8 (2.4-14.3) Bates E et al Obstet Gynecol 2010

  38. What are the Newborn Morbidities? • In the Shapiro-Mendoza et al study • Temperature instability • Hypoglycemia • Respiratory distress • Hyperbilirubinemia • Prolonged hospitalization • In the Wang et al study • Temperature instability • Hypoglycemia • Respiratory distress • Jaundice Shapiro-Mendoza CK et al Pediatr 2008; Wang ML & Dorer DJ Pediatr 2004

  39. Neonatal Resuscitation • Depends on gestational age AND mode of delivery • Near-term and term infants • Comparable 1 and 5 minute Apgar scores • Late preterm and term infants • 14% require more resuscitation interventions when delivered by elective c/section Wang ML & Dorer DJ Pediatr 2004; De Almelda MF et al J Perinatol 2007

  40. Respiratory Distress • For late preterm infants • Lungs are at the end of the terminal sac period of lung development • Synchrony and control of breathing is improving • Changes in epithelial sodium channels with length of gestation AND labor • Likely late preterm infant lung disease is a combination of delayed fluid absorption and surfactant insufficiency Jain L & Eaton DC Semin Perinatol 2006; Verklan MT Crit Care Nurs Clin North Am 2009

  41. Respiratory Distress • At delivery • 8% of 35-36 week infants required supplemental oxygen for at least 1 hour (3X’s the term rate) • Any respiratory distress incidence • 2004 study, late preterm have 9 times the odds of respiratory distress (28.9% vs. 4.2%) Escobar GJ et al Semin Perinatol 2006; Italian study; Wang ML & Dorer DJ Pediatr 2004

  42. Ventilation • Compared to 38-40 weeks gestation, likelihood of ventilation • 37 weeks: 2X • 36 weeks: 5X • 35 weeks: 9X • When delivered by c/section without labor, • 37 week infant had 5X the odds of severe respiratory morbidity compared to a 39 week infant delivered vaginally Escobar GJ et al Semin Perinatol 2006; Hansen AK et al BMJ 2008

  43. Temperature Instability • Late preterm infants have • Decreased • Brown fat • Hormonal regulation of brown fat breakdown • Subcutaneous fat • Increased • Body-surface area to body-weight ratio Fanaroff and Martin 2006; Polin and Fox 2003

  44. Hypothermia • Primary reason for NICU admission for 5.2% of late preterm infants • Hypothermia is associated with • Hypoglycemia • Respiratory distress/failure • Poor feeding • Sepsis evaluations Vachharajani AJ & Dawson JG Clin Pediatr 2009

  45. Hypoglycemia • Newborn glucose control • Hepatic glycogenolysis and gluconeogenesis • Late preterm infants • Immature hormonal control • Immature hepatic enzymes • Decreased hepatic glycogen stores • Immature ketogenic response increased risk for neurologic sequelae • Increased risk for cold stress and feeding difficulties Ramachandrappa A & Jain L Pediatr Clin North Am 2009; Verklan MT Crit Care Nurs Clin North Am 2009

  46. Hypoglycemia in Late Preterm Infants • Defined as <40 mg/dl in these studies • 8% of all neonates in the 1st 4 hours • Late preterm infants • 3X’s more likely • IV fluid support • 5% of term infants • 27% of 35-36 week infants Wang ML & Dorer DJ Pediatr 2004; Garg M & Devaskar SU Clin Perinatol 2006

  47. Sepsis Evaluations • Likelihood of sepsis screen with gestational age • Rates of sepsis evaluations • Late preterm infants 36.7% vs. 12.6% in term • 34 weeks 33% vs. 12% at 39 weeks • Only 0.4% of screened infants had culture-proven sepsis • Screened late preterm infants were • More likely to be treated with antibiotics • More likely to be treated longer Wang ML & Dorer DJ Pediatr 2004; McIntire DD et al Obstet Gynecol 2008

  48. Hyperbilirubinemia • Prematurity is associated with • Reduced hepatic uptake • Decreased conjugation • Decreased GI function and motility • Compounded by feeding difficulties Ramachandrappa A & Jain L Pediatr Clin North Am 2009; Verklan MT Crit Care Nurs Clin North Am 2009

  49. What’s the Risk? • Odds for developing serum bilirubin >20 mg/dl • 4 times greater for infant born at 36 weeks compared to infant born at 39-40 weeks • Likelihood of hospital readmission for phototherapy compared to infants ≥ 40 weeks gestation • 35-36 weeks: 13.2% • 36-37 weeks: 7.7% • 37-38 weeks: 7.2% Newman TB et al Pediatr 1999; Maisels MJ & Kring E Pediatr 1998

  50. Also, • Only one prospective study, • 35-37 week compared to 38-42 week infants were 2.4X more likely to develop “significant hyperbilirubinemia” • Nearly 25% of 35-37 week infants required phototherapy • Of concern, serum bilirubin was significantly higher for 35-37 week infants on Day 5 and Day 7 • For late preterm infants • Delayed bilirubin peak • Prolonged duration Sarici SU et al Pediatr 2004

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