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Preterm Labor and Birth

Preterm Labor and Birth. UNM Family Medicine Resident School 11/7/2018 Kira Paisley. Poll Everywhere TEXT: KIRAPAISLEY625 to 22333 once to join, then text your answers when it’s time. Learning Objectives. Understand key Epidemiology Answer the question “Why do we care?”

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Preterm Labor and Birth

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  1. Preterm Labor and Birth UNM Family Medicine Resident School 11/7/2018 Kira Paisley Poll Everywhere TEXT: KIRAPAISLEY625 to 22333 once to join, then text your answers when it’s time

  2. Learning Objectives • Understand key Epidemiology • Answer the question “Why do we care?” • Identify who is at RISK for preterm delivery • Identify evidence based PREVENTION strategies • Confidently DIAGNOSE and MANAGE initial presentation of Preterm Labor and PPROM

  3. OutpatientManagement OB Triage Management Identify risks Progesterone Cervical length screening Cerclage In-Patient Management Diagnosis Etiology Prognosis: FFN, Cervical length Post Partum Care Antenatal Corticosteroids Magnesium Antibiotics Tocolytics PPROM Neonatal care Maternal care

  4. Definitions • PRETERM LABOR: Contractions causing cervical change (dilation or effacement) prior to 37.0 weeks • Very early preterm – prior to 32 weeks • Early preterm – 32 0/7 to 33 6/7 weeks • Late preterm – 34 0/7 to 36 6/7 weeks • PPROM – preterm premature (or pre-labor) rupture of membranes • Premature Onset of Contractions – “POOC”, contractions without cervical change

  5. What causes Preterm Labor/Birth? • ~50% of cases are spontaneous labor without rupture of membranes • ~25% are PPROM • ~25 % are iatrogenic/indicated Spontaneous Labor at preterm thought to be result of infection or inflammation  Cytokines!

  6. Epidemiology • Preterm births decreased from 2007 -> 2014 • ACOG guidelines on prevention (ie: progesterone) • Decrease in teen pregnancy • Stricter guidelines on assisted reproductive technology (ie: fewer multiples) • Decline in medically non-indicated inductions prior to 39 weeks • Preterm births are increasing from 2014 -> 2017 • Late preterm births are culprit

  7. Martin JA, Osterman MJK. Describing the increase in preterm births in the United States, 2014–2016. NCHS Data Brief, no 312. Hyattsville, MD: National Center for Health Statistics. 2018.

  8. Source: Preterm birth rates are from the National Center for Health Statistics, 2017 final natality data. Grades assigned by March of Dimes Perinatal Data Center

  9. Source: Preterm birth rates are from the National Center for Health Statistics, 2017 final natality data. Grades assigned by March of Dimes Perinatal Data Center

  10. Source: Preterm birth rates are from the National Center for Health Statistics, 2017 final natality data. Grades assigned by March of Dimes Perinatal Data Center

  11. Neonatal Outcomes – Why do we care? Leading cause of infant mortality in the US • Morbidity • Respiratory disease: RDS, bronchopulmonary dysplasia • Cognitive: Cerebral palsy, intraventricular hemorrhage, developmental delay • GI: necrotizing enterocolitis • Risk of preterm delivery when an adult! Cost: A new study estimates employer-sponsored health plans spent at least $6 billion extra on infants born prematurely in 2013 Scott D. Grosse, Norman J. Waitzman, Ninee Yang, Karon Abe, Wanda D. Barfield. Employer-Sponsored Plan Expenditures for Infants Born Preterm. Pediatrics, 2017; e20171078 DOI: 10.1542/peds.2017-1078 Institute of Medicine (US) Committee on Understanding Premature Birth and Assuring Healthy Outcomes; Behrman RE, Butler AS, editors. Preterm Birth: Causes, Consequences, and Prevention. Washington (DC): National Academies Press (US); 2007. 10, Mortality and Acute Complications in Preterm Infants.Available from: https://www.ncbi.nlm.nih.gov/books/NBK11385/

  12. Shapiro-Mendoza CK, Barfield WD, Henderson Z, et al. CDC Grand Rounds: Public Health Strategies to Prevent Preterm Birth. MMWR Morb Mortal Wkly Rep 2016;65:826–830. DOI: http://dx.doi.org/10.15585/mmwr.mm6532a4

  13. OutpatientManagement OB Triage Management Identify risks Progesterone Cervical length screening Cerclage In-Patient Management Diagnosis Etiology Prognosis: FFN, Cervical length Post Partum Care Antenatal Corticosteroids Magnesium Antibiotics Tocolytics PPROM Neonatal care Birth control plan

  14. Name the Risk factors… • Poll Everywhere

  15. RISK factors for Preterm Delivery Rundell K, Panchal B. Preterm labor: prevention and management. Am. Fam. Physician. 2017;95:366–372.

  16. Ways to intervene? • Tobacco Cessation programs can help • Treatment of Asymptomatic bacteruria is successful • Screening and treatment for BV controversial • USPSTF says insufficient evidence • If symptomatic, should treat • Educate women on short interval pregnancy • Preconception control of chronic disease

  17. Progesterone • Contributes to pregnancy in multiple ways: • Functional withdrawal of progesterone  occurs around onset of labor • Prevents apoptosis in fetal membrane explants under pro-inflammatory conditions  ?alteration of immune response 2013 – Data became overwhelming that Progesterone prevents Preterm Birth

  18. Progesterone • 2013 Meta-analysis with 39 randomized trials; treatment with progesterone showed LOWER RISK for: • Birth < 34 weeks, RR 0.31 • Birth < 37 weeks, RR 0.55 • Neonatal death, RR 0.45 • Use of assisted ventilation in neonate, RR 0.40 • Necrotizing enterocolitis in neonate, RR 0.30 • NICU admission, RR 0.24

  19. Progesterone – Recommended! For PREVENTION of Preterm Birth Singleton pregnancy with prior preterm birth (<37 weeks) IM progesterone recommended • 17 Alpha-HydroxyprogesteroneCaproate) 250mg IM weekly • Requires a prior auth, so work with your RN • Home or in-clinic injections, can get through home health • Initiate between 16-24 weeks, until 36 weeks Missed doses may increase risk of Preterm Birth – pts should be counseled prior to starting

  20. Figure 3. Estimated Probability of Spontaneous Preterm Delivery before 35 Weeks of Gestation from the Logistic-Regression Analysis (Dashed Line) and Observed Frequency of Spontaneous Preterm Delivery (Solid Line) According to Cervical Length Measured by Transvaginal Ultrasonography at 24 Weeks. Cervical Length screening • Risk of PTB is inversely proportional to cervical length Birth <35 weeks for: • 30% in women with CL 20–24 mm • 50% with CL 10–19 mm • 90% with CL <10 mm • Birth <35 weeks only 16% in women with CL > 25 mm Iams JD, Goldenberg RL, Meis PJ, Mercer BM, Moawad A, Das A, et al. The length of the cervix and the risk of spontaneous premature delivery. National Institute of Child Health and Human Development maternal fetal medicine unit network. N Engl J Med. 1996;334:567–72. Iams J. Identification of candidates for progesterone. ObstetGynecol 2014;123:1317-1326

  21. Cervical Length screening • Society of Maternal-Fetal Medicine, ACOG recommendations “Routine transvaginal cervical length screening for women with singleton pregnancy and history of prior spontaneous preterm birth” Grade 1A Routine screening = trans-vaginal, 16-22 weeks (q1-2 weeks) Do NOT screen if: • Cerclage in place - multiple gestations • PPROM - Placenta previa Society of Maternal Fetall Medicine, McIntosh, J., Feltovich, H, Berghella, V., Manuck, T. “SMFM Consult Series #40: The role of routine cervical length screening in selected high and low-risk women for preterm birth prevention.” AJOG. 9/2016.

  22. What about Vaginal Progesterone? • Does NOT reduce risk of PTB in women with hx of PTB in absence of short cervix • OPPTIMUM and PROGRESS trial Women with hx of PTB AND Cervical length <25mm • 2018 Systemic review • Reduced risk of PTB, Neonatal morbidity and mortality in singleton gestations with CL <25mm Romero, R. Conde-Agudelo, A. Da Fonseca, E. O’Brien, JM, Cetingoz, E. Creasy, GW. Hassan, SS. Nicolaides, KH. “Vaginal Progesterone for preventing preterm birth and adverse perinatal outcomes in singleton gestations with a short cervix: a meta-analysis of individual patient data.” Am J Obstet Gynecol. 2018;218(2):161.

  23. Cerclage placement Who qualifies? • Women with CL <25mm before 24wks AND • History of preterm birth <34 weeks Work with OB colleague American College of Obstetricians and Gynecologists ACOG practice bulletin no.142: cerclage for the management of cervical insufficiency. Obstet Gynecol. 2014;123:372–379.

  24. Out Patient Management Cases!

  25. OutpatientManagement OB Triage Management Identify risks Progesterone Cervical length screening Cerclage In-Patient Management Diagnosis Etiology Prognosis: FFN, Cervical length Post Partum Care Antenatal Corticosteroids Magnesium Antibiotics Tocolytics PPROM Neonatal care Birth control plan

  26. OB Triage Management It’s your first shift as a 2nd year Night Float on MCH. You’re senior is delivering their continuity in another room. You get a page from triage: “36 yo G1 at 34 wks contracting, she looks uncomfortable…”

  27. OB Triage Management • Don’t panic • Assess the patient as soon as you can • Involve your Attending/Senior Resident early • Consider the following 5 key questions…

  28. Other key thing: • Scan to be sure VERTEX Rundell K, Panchal B. Preterm labor: prevention and management. Am. Fam. Physician. 2017;95:366–372.

  29. OB Triage Management What is the likelihood she’ll delivery preterm? • Fetal Fibronectin - Negative predictive value 99% for delivery within 14 days - Positive predictive value 13-30% for delivery in 7-10 days - Can only be done if NOTHING in vagina in past 24hrs - False positives with amniotic fluid, blood, vaginal infection - Collect FIRST on your speculum exam

  30. OB Triage Management What is the likelihood she’ll deliver preterm? Cervical Length can help stratify risk - involve OB for imaging - more reliable with FFN than either alone - Reassuring if >3cm (1% delivery in 7 days in one study)

  31. OB Triage Management 36 yo G1 at 34 wks contracting, she looks uncomfortable… You confirm her dating, she’s 34w1d SSE, negative for SROM FFN collected and sent UA shows +nitrites, +LE, ketones Toco shows contractions q3-5 min, reactive NST 11:55PM -- SVE 1cm/50%/-2 QUESTIONS 1. Is she less than 37 weeks? 2. Is she ruptured? 3. Is she in labor? 4. Is there an infection? 5. What’s the likelihood she’ll delivery preterm?

  32. OB Triage Management You give her 1L bolus of fluids FFN comes back Negative 0230 AM: SSE 1/50%/-2 Her contractions are now q10 min, mild Now what?  Send her home, treat for UTI • Premature onset of Contractions without cervical change, “POOC” • only 18% delivery before 37 wks • only 3% delivery within 2 weeks of triage visit ACOG Practice Bulletin 171, October 2016. Management of Preterm Labor

  33. OutpatientManagement OB Triage Management Identify risks Progesterone Cervical length screening Cerclage In-Patient Management Diagnosis Etiology Prognosis: FFN, Cervical length Post Partum Care Antenatal Corticosteroids Magnesium Antibiotics Tocolytics PPROM Neonatal care Birth control plan

  34. In-Patient Management It’s your second shift as a 2nd year Night Float on MCH. You’ve sent your senior to go nap because you’re feeling confident. Page from triage: 22 yo G5 P1304 at 31 weeks is presenting with painful contractions…

  35. In-Patient Management • You don’t panic • You alert your attending • You go see the patient • Evaluation: • SSE neg pooling, no ferning, negnitrizine; cervix looks slightly open • GBS, FFN, STD Amp collected; UDS, Ucx and UA sent, UDATR sent • Toco with q2-3 min contraction, reactive NST • Vertex on US

  36. In-Patient Management QUESTIONS 1. Is she less than 37 weeks 2. Is she ruptured? 3. Is she in labor? 4. Is there an infection? 5. What’s the likelihood she’ll delivery preterm? • SVE (backed up by Attending) 3cm/50%/-2 at 0100 • You order IV fluids • Her FFN comes back POSITIVE • OB helps you do a cervical length and it’s 1.5cm • Her UDATR comes back + for methamphetamines 1 hour later… SVE – 3 cm/80%/-1 Admit to L&D for Preterm Labor!

  37. In-Patient Management

  38. In-Patient Management • 30% of preterm labor resolves spontaneously • 50% of women admitted for PTL actually birth at term Interventions must benefit the baby - must be viable - prolonging pregnancy is better than immediate delivery

  39. Antenatal Corticosteroids • Improves neonatal outcomes • Decreases: • Mortality • Incidence and severity of RDS • Intraventricular hemorrhage • Necrotizing enterocolitis • Single course 24.0-33.6 wks at risk of delivery within 7 days • Betamethasone 12mg IM q24hrs x 2 doses • Dexamethasone 6mg IM q12 hr x 4 doses Roberts  D, Brown  J, Medley  N, Dalziel  SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database of Systematic Reviews 2017, Issue 3. Art. No.: CD004454. DOI: 10.1002/14651858.CD004454.pub3.

  40. Rescue dose Steroids • Studies have shown reduction in Respiratory Distress Syndrome ACOG recommends: • Single repeat course of corticosteroids • < 34 0/7 weeks • At risk of delivery within 7 days • Prior antenatal corticosteroid course was >14 days ago In PPROM, rescue dose steroids is controversial Garite TJ, Kurtzman J, Maurel K, Clark R. Impact of a ‘rescue course’ of antenatal corticosteroids: a multi-center randomized placebo-controlled trial. Obstetrix Collaborative Research Network [published erratum appears in Am J ObstetGynecol 2009;201:428]. Am J ObstetGynecol 2009;200:248.e1–9. (Level I)

  41. Late Preterm Steroids • MFMU Network Antenatal Late Preterm Steroids trial • Double-blind, placebo controlled RCT • Excluded – multiple gestations, Pre-gestational diabetes, previous steroids, chorio • Tocolysis was not used Primary outcome: decreased need for respiratory support However – increased hypoglycemia in neonate ACOG Committee Opinion from 2017 recommends - Single course of Betamethasone for women 34 0/7 – 36 6/7 at risk of preterm birth within 7 days Gyamfi-Bannerman C, Thom EA, Blackwell SC, Tita AT, Reddy UM, Saade GR, et al. Antenatal betamethasone for women at risk for late preterm delivery. NICHD Maternal-Fetal Medicine Units Network. N Engl J Med 2016;374:1311–20. ACOG Committee Opinion, Number 713. August 2017. Antenatal Corticosteroid Therapy for Fetal Maturation.

  42. Magnesium Cochrane Review • Neuroprotection for delivery < 32 weeks • Outcomes - Reduction in cerebral palsy, RR 0.68 • No evidence for any specific regimen • UNM 4g loading dose, then 1 g/hr infusion • No evidence that IV Mg prolongs pregnancy Shepherd  E, Salam  RA, Middleton  P, Makrides  M, McIntyre  S, Badawi  N, Crowther  CA. Antenatal and intrapartum interventions for preventing cerebral palsy: an overview of Cochrane systematic reviews. Cochrane Database of Systematic Reviews 2017, Issue 8. Art. No.: CD012077. DOI: 10.1002/14651858.CD012077.pub2. Costantine MM et al. Effects of antenatal exposure to magnesium sulfate on neuroprotection and mortality in preterm infants. NICHD MFM Units Network ObstetGynecol 2009;114:354-364. Magnesium sulfate before anticipated preterm birth for neuroprotection. ACOG Committee Opinon 455. ACOG and SMFM.

  43. Tocolytics • Used to allow time to give steroids and magnesium, arrange transport if needed Contraindications • Pre-viability • IUFD • Lethal anomaly • Non reassuring fetal status • Chorioamnionitis • Pre-eclampsia with severe features, eclampsia • Hemodynamic instability of mother • PPROM • Maternal contraindications

  44. Tocolytics • Reduces birth within 48hrs, but does not improve neonatal outcomes • No evidence of maintenance therapy outside 48-72 hr window while inpatient and many risks • Magnesium should not be used as a tocolytic • When using for neuroprotection, be aware of interactions with tocolytics

  45. Tocolytics Rundell K, Panchal B. Preterm labor: prevention and management. Am. Fam. Physician. 2017;95:366–372.

  46. Antibiotics • Despite bacterial infections presumed cause for majority of preterm births >32 weeks… • There is no evidence antibiotic therapy prolongs pregnancy or reduces neonatal morbidity or mortality • And there may be some evidence of harm King et al. Prophylactic antibiotics for inhibiting preterm labor with intact membranes. Cochrane Database 2002, Issue 4.

  47. Antibiotics • Meant for prevention of GBS sepsis in newborn only • CDC Recommendations • Penicillin G: 5 million units IV, then 2/5 million units IV q 4 hours until delivery • “Adequate” treatment is >4hrs/2 doses • Low risk PCN allergy: Cefazolin 2g IV, then 1gIV q 8 hours until delivery • High risk PCN allergy, GBS susceptibilities known: Clindamycin 900mg IV q 8 hours until delivery • High risk PCN allergy, GBS susceptibilities unknown: Vancomycin 1g IV q 12 hours until delivery

  48. In-Patient Management • 22 yo G5 P1304 at 31.0 wks • Admitted for cervical change from 3/50/-2  3/80/-1 • Pregnancy has been otherwise complicated by amphetamine use, hx of UTI in early pregnancy without confirmed TOC; no allergies to medications • What interventions are indicated? • Steroids! • IV Mg for neuroprotection • PCN for GBS prophylaxis • Consider tocolysis to get her through steroid window • NICU consult

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