1. Intrauterine Infections Justin Sanders MD Dept. Family and Social Medicine Albert Einstein College of Medicine June 25, 2009

2. Case 34 G6P1041 GBS+ at 40 1/7 weeks  Pt receiving intrapartum PCN  Prolonged labor augmented with Pitocin  Pain control with epidural  MD notices pt feels warm at the time of delivery  Temp 101.5 F

3. Objectives Define Intrauterine Infection Diagnosis Differential Diagnosis for peripartum fever Epidemiology Risk factors Etiology/Pathophysiology Sequelae Prevention Management

4. Intrauterine Infection Puerperal infection – can be defined clinically or histopathologically. Can be found in subclinical form Includes infection of amniotic fluid, fetal membranes, placenta and/or decidua Often referred to generally as chorioamnionitis or “chorio” Also includes deciduitis, villitis (placental villi), and funisitis (umbilical cord)

5. Goldenberg R et al. N Engl J Med 2000;342:1500-1507 Potential Sites of Bacterial Infection within the Uterus Intrauterine Infection

6. Diagnosis Clinical – Temp ≥ 38°C (100.4°F) – ≥ 2 of: maternal tachycardia, fetal tachycardia, uterine tenderness, foul odor of the amniotic fluid, maternal leukocytosis Histopathologic – Inspection of placenta and fetal membranes Identification of polymorphonuclear lympocytes in tissue – Amniocentesis – Occurs with much higher incidence than clinical intrauterine infection

7. Differential Diagnosis Epidural anesthesia – Strongly associated with intrapartum maternal fever (RR 5.6, 95%CI, 4.0-7.8, p<.001), neonatal sepsis workup, and neonatal antibiotics – but not with neonatal sepsis Dehydration Urinary tract infection Genital tract infection Malignant Hypertension (theoretical, Ψ assoc.)

8. Epidemiology Clinical – Term: 0.5-2%; Preterm 0.5-10% – Determined mostly by older studies Histological – 2-3 x incidence of clinical infection – 5-30% > 34wks; 40-50% 29-34 wks; – Nearly all fetal membranes of preterm labors <28 weeks (60-80%)

9. Risk Factors Independent Risk Factors – Nulliparity – (P)PROM / Preterm Labor – Duration of Labor – Duration of ROM – Internal fetal monitors – Number of vaginal examinations ! ! ! Others – Young age – Low SocioEconomic Status – BV – GBS + – Meconium-stained amniotic fluid

10. Pathogenesis Most common: ascending bacteria from lower genital tract. Polymicrobial – usually a combination of anaerobic and aerobic organisms. Pathogens most frequently isolated from amniotic fluid of pts with “chorio” are found in vaginal flora: – Gardnerella, Ureaplasma, Bacteroidies, Mycoplasma, group A, B, C strep, Peptococcus, Peptostreptococcus, E. Coli.

11. Pathogenesis Other (rare) routes of infection: hematogenous, transplacental, retrograde from pelvis, transuterine infection from medical procedures (CVS, amniocentesis) Believed to be endotoxin mediated effect that may initiate maternal/fetal inflammatory response → PROM, PTL, neurologic damage in fetus

13. Sequelae: Labor – (P)PROM – subclinical infection – Decreased uterine contractility C-Section for FTP despite Oxytocin AOL Satin et al: – pts w/ chorio dx'd prior to Pit AOL had shorter intervals from start Pit to delivery – Pts w/ chorio dx'd after Pit AOL, interval to delivery significantly prolonged – Postpartum hemorrhage 50% greater after C-section; 80% greater after SVD Bottom Line: Increased Labor Abnormalities

14. Goldenberg R et al. N Engl J Med 2000;342:1500-1507 Potential Pathways from Choriodecidual Bacterial Colonization to Preterm Delivery IUI and PTL

15. Sequelae: Newborn Complications of Preterm delivery – Fetal lung immaturity, IVH, PVL, seizures (3- fold risk in one study) Low Apgars, hypotension, need for resuscitation at time of delivery. Bacteremia and Sepsis Cerebral Palsy (independent RF, pre + term) – OR 9.3 in one study – Assoc. w/ PVL (in turn assoc. w/ high IA cytokine levels)

16. Sequelae: Newborns Wendel et al, 1994: Chorioamnionitis, Non- reassuring FHT, Neonatal outcome – Background: Nonreassuring FHT, e.g. tachycardia and dec. variability, common in presence of acute chorio – 217 pts with chorio; analyzed FHT, compared with duration of time from dx to delivery, neonatal outcomes – No diff. In cord pH, Apgar scores, sepsis, admission to special-care nursery, O2 req in neonates, especially under 12 hours

17. Prevention Treat BV? – Cochrane review: no improvement in outcomes – ? benefit to early (<20wks) treatment – Nevertheless, CDC recommends Treat Trichomoniasis? – RF for (P)PROM, PTL/PTB – No recommendation Treat GBS! – Leading cause of neonatal sepsis

18. Prevention Avoid digital vaginal examination if possible in patients with PPROM and PROM – ACOG advises against DVE during intial eval unless prompt labor/delivery anticipated. – Visual estimation with sterile speculum is recommended to assess cervical status Minimize DVE in labor, esp in latent phase labor and/or ROM Avoid IUPC's unless needed to dx arrest disorders

19. Management Centers on effective delivery and administration of broad-spectrum abx Gentamycin 1.5mg/kg q8h, plus Ampicillin 2G q6h or penG 5mU q6 Anaerobic coverage for C-section – Clindamycin or Metronidazole Other (context dependent) choices: Ext-spectrum penicillins (eg. Pipercillin/Tazobactam) Cephalosporins (e.g. cefotetan) Vancomycin for PCN allergy

20. Management Start abx ASAP after diagnosis – Longer dx to delivery interval (p<.001) – Decreased neonatal sepsis (p<.001) – Lower neonatal sepsis related mortality (p<.15) Duration of tx – Traditionally 48-72h – Short course appears to be sufficient One study studied intrapartum plus one postpartum dose of each agent = abx tx until 24hours afebrile

21. Management Antipyretics – Advisible for fetal indications – Maternal temp related to fetal acid-base balance Delivery indicated, not necessarily C-section Placenta to path, cord gasses sent (and followed up on)

22. Case Amp 2g and Gent 80mg initiated immediately Clinical suspicion low after delivery Abx held after one dose post-partum Mom and baby did well

23. Summary More than a fever Remember the epidural Fairly common Don't touch too much Prevention is better than treatment Treat early (but not necessarily long) Placenta to path

24. References Churgay C, Smith M, Blok B. Maternal Fever During Labor – What does it mean? J Am Board Fam Pract 1994;7:14-24 Edwards R. Chorioamnionitis and Labor. Obstetrics and Gynecology Clinics of N America 2005;32:287-96 Fahey J. Clinical management of Intra-amniotic Infection and Chorioamnionitis: A Review of the Literature. J Midwifery Womens Health 2008;53:227–235 Goldenberg R, Hauth J, Andrews W. Intrauterine Infection and Preterm Delivery. N.Engl J Med 2000;342:1500-1507 Lieberman E. Epidural analgesia, intrapartum fever, and neonatal sepsis evaluation. Pediatrics 1997;99:415-19 Marowitz A. Midwifery Management of Premature Rupture of Membranes at Term. J Midwifery Womens Health 2007;52:199–206 Satin A et al. Chorioamnionitis: a harbinger of dystocia. Obstet Gynecol 1992;79:913-5 Simhan H, Canavan T. Preterm Premature Rupture of Membranes: diagnosis, evaluation and management strategies. BJOG: Int J Obstetrics and Gynaecology 2005;112(S1):32-37 Snyder M, Crawford P, Jamieson B. What treatment approach to intrapartum maternal fever has the best fetal outcomes? J Fam Pract 2007;56(5) Wendel P et al. Chorioamnionitis: Associations of Nonreassuring Fetal Heart-Rate Patterns and Interval From Diagnosis to Delivery on Neonatal Outcome. Infectious Disease in Obstetrics and Gynecology 1994;2:162-166