1. Prematurity Labor, Delivery Muruvet Elkay, MD PL-II12/16/2005

2. Objectives Epidemiology Epidemiology Risk factors Risk factors Infection Infection Role of antenatal steroids Role of antenatal steroids Complications Complications Management Management

3. Preterm Labor Preterm labor (PTL): Presence of contractions which cause progressive effacement and dilatation of the cervix between 20 and 37 weeks’ gestation. Preterm labor (PTL): Presence of contractions which cause progressive effacement and dilatation of the cervix between 20 and 37 weeks’ gestation. Preterm birth (PB): Occurs in 6-8% of pregnancies. The incidence has remained stable for more than 25 years. Preterm birth (PB): Occurs in 6-8% of pregnancies. The incidence has remained stable for more than 25 years. Ref: eMedicine Sep 22, 2004: Preterm Labor: Article by Edward R. Newton, MD Ref: eMedicine Sep 22, 2004: Preterm Labor: Article by Edward R. Newton, MD

4. Terms Related to Prematurity Premature infant: An infant born before 37 weeks of estimated GA. Premature infant: An infant born before 37 weeks of estimated GA. Low birth weight (LBW): BW<2,500 g Low birth weight (LBW): BW<2,500 g Very low birth weight (VLBW): BW<1,500 g Very low birth weight (VLBW): BW<1,500 g Extremely low birth weight (ELBW): BW<1,000 g Extremely low birth weight (ELBW): BW<1,000 g Chronologic or birth age: Time since birth. Chronologic or birth age: Time since birth. GA: Estimated time since conception; postconceptional age. GA: Estimated time since conception; postconceptional age. Corrected age: Age corrected for prematurity. Corrected age: Age corrected for prematurity. Ref: David E. Trachtenbarg etal. American Family Physician 1998; 57 (9): 1-11

5. The Epidemiology of Preterm Birth Racial differences in the rate of preterm Racial differences in the rate of preterm LBW VLBW LBW VLBW African-American women 13.0% 3.1% Asian-Pacific Islanders 7.3 1.0 Native Americans 6.8 1.2 Whites 6.5 1.1 Hispanics 6.4 1.1 In a twin, triplet or higher order multiple gestation: 23 % of LBW infants In a twin, triplet or higher order multiple gestation: 23 % of LBW infants Ref: Jay D. Iams, Clin Perinatol 30 (2003) 651-664. Ref: Jay D. Iams, Clin Perinatol 30 (2003) 651-664.

6. Ref: Edward R. Newton: Clin Perinatol 32 (2005) 571-600. US Incidence of Preterm Birth 1992-2002

7. Neonatal Morbidity and Mortality by Gestational Age Ref: Edward R. Newton: Clin Perinatol 32 (2005) 571-600.

8. Hospital Charges by Gestational Age of Delivery Ref: Edward R. Newton: Clin Perinatol 32 (2005) 571-600. GA (n) Mother Charges Baby Charges Total Charges 25-26 weeks (40) $11,102$192,882$203,994 27-28 weeks (58) $9,765$160,234$169,999 29-30 weeks (76) $10,882$70,684$81,566 31-32 weeks (127) $9,500$36,991$46,490 33-34 weeks (208) $9,016$15,450$24,447 35-36 weeks (240) $6,091$8,484$14,457 >36 weeks (204) $4,310$2,276$6,586

9. Etiology of Preterm Birth Physician-initiated birth (indicated PB): Physician-initiated birth (indicated PB): a. Pre-eclampsia 40% b. Fetal distress 30% c. IUGR 10% d. Abruption placenta or placenta previa 10% e. Fetal death 5% Spontaneous PB: Spontaneous PB: a. Preterm labor (PTL) b. Preterm premature rupture of membranes (PPROM) Ref: Edward R. Newton: Clin Perinatol 32 (2005) 571-600

10. PTL Previous PB Previous PB Low body mass Low body mass Poor weight gain Poor weight gain Heavy work load Heavy work load Uterine abnormalities Uterine abnormalities Drug abuse, smoking Drug abuse, smoking PPROM INFECTION Uterine distension Cervical incompetence African-American Low socioeconomic class Drug abuse, smoking Risk Factors for PTL and PPROM Ref: Edward R. Newton: Clin Perinatol 32 (2005) 571-600.

11. The Strong Association Between Infection and Preterm Birth Incidence of subclinical histologic chorioamnionitis: Incidence of subclinical histologic chorioamnionitis: 50%24 to 28 weeks 50%24 to 28 weeks 10%>37 weeks 10%>37 weeks The smaller the fetus, the more likely the chorioamnion cultures are positive: The smaller the fetus, the more likely the chorioamnion cultures are positive: 80%<1000 g 30% >2500 g Ref: Edward R. Newton: Clin Perinatol 32 (2005) 571-600.

12. GenomeUteroplacental Insufficiency Bacteria, Virus, Protozoa Infection:Leukocyte Response Fetal StressMaternal Stress ↓Progesterone Inhibition↑TOLL 4 Receptors Cytokine Cascade:↑TNF, ↑IL6, ↑ IL8, etc Decidual Activation Genome Phospholipase A, prostaglandins, lysolethecin, mettaloproteinases, collagenases, elastases.. Relation of Infection and Preterm Birth

13. Preterm Labor PRETERM BIRTH Rupture of MembraneCervical Incompetence Phospholipase A, prostaglandins, lysolethecin, mettaloproteinases, collagenases, elastases.. Ref: Edward R. Newton: Clin Perinatol 32 (2005) 571-600

14. Risk Factors for Infection-Related Preterm Birth Ref: Edward R. Newton: Clin Perinatol 32 (2005) 571-600. Historical: Historical: Idiopatic PL, PROM History of UTI and STI Behavioral: Behavioral: Unintended pregnancy Unmarried Multiple partner Signs and symptoms: Signs and symptoms: Vaginal discharge Dysuria, dyspareunia

15. Prophylactic Antibiotics to Prevent Preterm Birth GBS Incidence of vaginal GBS- 20-25%. Incidence of vaginal GBS- 20-25%. No association between vaginal GBS and PB. No association between vaginal GBS and PB. Prophylactic antibiotics are not indicated for recto-vaginal colonization of GBS. Prophylactic antibiotics are not indicated for recto-vaginal colonization of GBS. Antepartum treatment of GBS in urine. Antepartum treatment of GBS in urine. Ref: Edward R. Newton: Clin Perinatol 32 (2005) 571-600.

16. Therapeutic Antibiotics for Infection- Related Preterm Birth GBS: Antepartum treatment of all the women with the risk factors: Maternal colonization Maternal colonization Previous infant who had GBS sepsis Previous infant who had GBS sepsis Antenatal GBS asymptomatic bacteriuria Antenatal GBS asymptomatic bacteriuria ROM >12 hrs ROM >12 hrs Intrapartum fever (probable chorioamnionitis) Intrapartum fever (probable chorioamnionitis) GA < 37 wks GA < 37 wks Ref: Edward R. Newton: Clin Perinatol 32 (2005) 571-600.

17. Antibiotics for Inhibiting PL with Intact Membranes Antibiotics are not recommended. Antibiotics are not recommended. Ref: Edward R. Newton: Clin Perinatol 32 (2005) 571-600.

18. Antibiotics for PPROM Risk of chorioamnionitis- 20% between 28 and 34 weeks. Antibiotics are recommended in nonlaboring women. Ref: Edward R. Newton: Clin Perinatol 32 (2005) 571-600.

19. Chorioamnionitis Inflammation or infection of the placenta, chorion, and amnion. Inflammation or infection of the placenta, chorion, and amnion. Histologic, subclinical chorioamnionitis: Histologic, subclinical chorioamnionitis: >50% of preterm deliveries <20% of term deliveries Clinical chorioamnionitis: Clinical chorioamnionitis: 5% to 10% of preterm deliveries 1% to 2% of term deliveries 1% to 2% of term deliveries Ref: Rodney K Edwards: Obstet Gynecol Clin N Am 32 (2005) 270-296.

20. Clinical Chorioamnionitis Most frequent identifiable cause of PL. Most frequent identifiable cause of PL. <30 weeks 50% PPROM 40% PL with intact membranes 30% Maternal fever in the peripartum 10% to 40% Polymicrobial. Polymicrobial. Ref: Rodney K Edwards: Obstet Gynecol Clin N Am 32 (2005) 270-296.

21. Clinical Chorioamnionitis Diagnostic criteria: Maternal fever of greater than 100.4 F and at least 2 of the following conditions: Maternal leukocytosis (>15,000 cells/cubic mm) Maternal leukocytosis (>15,000 cells/cubic mm) Maternal tachycardia (>100 bpm) Maternal tachycardia (>100 bpm) Fetal tachycardia (>160/bpm) Fetal tachycardia (>160/bpm) Uterine tenderness Uterine tenderness Foul odor of the AF Foul odor of the AF Ref: Rodney K Edwards: Obstet Gynecol Clin N Am 32 (2005) 270-296.

22. Neonatal Outcomes of Chorioamnionitis Intraventricular hemorrhage Intraventricular hemorrhage Periventricular leukomalacia Periventricular leukomalacia Cerebral palsy Cerebral palsy Increased rates of bacteremia Increased rates of bacteremia Clinical sepsis Clinical sepsis Increased mortality Increased mortality Low Apgar scores Low Apgar scores Hypotension Hypotension The need for resuscitation at the delivery The need for resuscitation at the delivery Neonatal seizures Neonatal seizures Ref: Rodney K Edwards: Obstet Gynecol Clin N Am 32 (2005) 270-296.

23. Antenatal Steroids Indicated in the delivery of a fetus at 24-34 weeks’ gestation in the absence of clinical infection. Indicated in the delivery of a fetus at 24-34 weeks’ gestation in the absence of clinical infection. Delay of delivery- A minimum of 12 hours. Delay of delivery- A minimum of 12 hours. Duration of benefits-7 days or more? Duration of benefits-7 days or more? Betamethasone or Dexamethasone? Betamethasone or Dexamethasone? Reduces the incidence of IVH and NEC. Reduces the incidence of IVH and NEC. An adverse impact of multiple courses on fetal growth and development. An adverse impact of multiple courses on fetal growth and development. Ref: eMedicine Sep 22, 2004: Preterm Labor: Article by Edward R. Newton, MD.

24. Benefits of Antenatal Steroids Last 7 Days or More? 197 neonates 197 neonates Group I: 98 delivered within 7 days Group I: 98 delivered within 7 days Group II: 99 delivered more than 7 days Group I: Lower incidence of receiving respiratory support more than 24 hrs. Group I: Lower incidence of receiving respiratory support more than 24 hrs. No significant differences between the groups in other measures of neonatal morbidity. No significant differences between the groups in other measures of neonatal morbidity. Ref: Alan M. Peaceman et al. Am J Obstet Gynecol 2005; 193, 1165-9.

25. Betamethasone or Dexamethasone 201 preterm singleton infants 201 preterm singleton infants GA between 24 and 34 weeks GA between 24 and 34 weeks Neurodevelopmental outcome at 2 years corrected age Neurodevelopmental outcome at 2 years corrected age Results: Multiple antenatal courses of DEXAMETHASONE associated with an increased risk of leukomalacia and 2-year infant neurodevelopmental abnormalities. Results: Multiple antenatal courses of DEXAMETHASONE associated with an increased risk of leukomalacia and 2-year infant neurodevelopmental abnormalities. Ref: Spinillo A et al. Am J Obstet Gynecol 2004;191 (1): 217-24. Ref: Spinillo A et al. Am J Obstet Gynecol 2004;191 (1): 217-24.

26. Complications of Premature Infants RDS RDS IVH IVH NEC NEC ROP ROP CLD (BPD) CLD (BPD) Infection Infection Anemia Anemia PDA PDA Apnea Apnea Cryptorchidism Cryptorchidism Inguinal hernia Inguinal hernia Umbilical hernia Umbilical hernia

27. SGA and IUGR: Are They Synonymous? SGA: Birth weight below the 10 th percentile for GA or > 2 standart deviations below the mean for GA. SGA: Birth weight below the 10 th percentile for GA or > 2 standart deviations below the mean for GA. IUGR: A process that causes a reduction in an expected pattern of fetal growth. IUGR: A process that causes a reduction in an expected pattern of fetal growth. 1. Symmetric IUGR 2. Asymmetric IUGR (head-sparing IUGR): All IUGR infants may not be SGA (Ponderal index). All IUGR infants may not be SGA (Ponderal index). Ref: Utpala G et al: Pediatr Clin N Am 2004;51: 639-654.

28. Neonatal Complications of IUGR or SGA Metabolic disorders: Hypoglycemia, hypocalcemia Metabolic disorders: Hypoglycemia, hypocalcemia Hypothermia Hypothermia Hematologic disorders: polycytemia Hematologic disorders: polycytemia Hypoxia: birth asphyxia, meconium aspiration, persistent fetal circulation Hypoxia: birth asphyxia, meconium aspiration, persistent fetal circulation Congenital malformation Congenital malformation Ref: Utpala G et al: Pediatr Clin N Am 2004;51: 639-654.

29. Long-term Complications of IUGR or SGA Cardiovascular disease Hypertension Type 2 diabetes Ref: Utpala G et al: Pediatr Clin N Am 2004;51: 639-654

30. A Premature Infant may be a SGA or IUGR Infant Also- Double Jeopardy! An adverse outcome resulting from both immaturity and deficient intrauterine growth. An adverse outcome resulting from both immaturity and deficient intrauterine growth. Increased risk for mortality and major neonatal morbidities, including RDS, BPD, ROP, and NEC. Increased risk for mortality and major neonatal morbidities, including RDS, BPD, ROP, and NEC. Intensified complications of prematurity by the effect of suboptimal fetal growth. Intensified complications of prematurity by the effect of suboptimal fetal growth. Ref: Rivka H. Regev et al: Clin Perinatol 2004; 34: 453-473.

31. Management of Premature Infants Delivery room management Delivery room management Temperature and humidity control Temperature and humidity control Fluids and electrolytes Fluids and electrolytes Blood glucose Blood glucose Calcium Calcium Nutrition Nutrition Respiratory support Surfactant PDA Transfusion Skin care Other special considerations

32. THANK YOU Special Thanks to Dr. Manuel V. and Colin Bird MSIII