Preterm Labor 2021 Update

Preterm labor is the labor that starts before the 37th completed week. In this presentation, we will discover causes, pathogenesis, diagnosis, clinical features, and management principles for preterm labor along with the most recent evidence.

1. PRETERM LABOR Presented by: Dr. Aryan ( Anish Dhakal) 5 th MARCH, 2021

2. Introduction Labor starts before the 37 th completed weeks (<259 days) Also called Preterm Parturition syndrome Prevalence: 10-15 % 70-80% are spontaneous Significant cause of perinatal morbidity and mortality

3. Subtypes of Preterm Birth 3

4. 4

5. 5

6. 6

7. 7 PATHOGENESIS

8. 8

9. Prodromal Symptoms/Signs of Preterm Labor Menstrual-like cramping Mild , irregular contractions Low back ache Pressure sensation in the vagina or pelvis Vaginal discharge of mucus; clear , pink, or slightly bloody (i.e. mucus plug, bloody show) Spotting , light bleeding

10. Predictors of Preterm labor Clinical predictors Multiple pregnancy History of prior preterm b irth Presence of genital tract infection Symptoms of Preterm Labor Biophysical predictors Uterine contraction Bishop score (≥4 ) Cervical length Biochemical predictors Fetal fibronectin in cervicovaginal discharge Others IL-6,8 ; TNF α Placental alpha-microglobulin-1 (PAMG-1) or phosphorylated insulin-like growth factor binding protein-1 (pIGFBP-1) are under trials

11. Diagnosis Uterine contractions (≥4 every 20 minutes or ≥8 in 60 minutes)   plus Cervical dilation ≥3 cm  or Cervical length <20 mm on transvaginal ultrasound  or Cervical length 20 to <30 mm on transvaginal ultrasound and positive fetal fibronectin ( fFN )

12. 12 Prior PTB is the strongest risk factor for future PTB, and recurrences often occur at the same gestational age . In other words, chances of preterm birth is inversely proportional to the number of prior term births.

13. 13

14. 14

15. 15

16. 16

17. 17

18. 18

19. 19

20. Investigations CBC, CRP Urine for routine analysis, culture/ censitivity Cervicovaginal swab (culture and fetal fibronectin ) Ultrasonography (fetal well being, cervical length and placental localization) Serum electrolytes and glucose levels (tocolytic agents toxicity)

21. Management 1. To prevent preterm onset of labor, if possible 2. To arrest preterm labor, if not contraindicated 3. Appropriate management of labor 4. Effective neonatal care

22. Prevention of PTL Primary : reducing high risk factors (e.g. infection) Secondary : screening tests for early detection and prophylactic treatment (e.g. Tocolytics) Tertiary : reducing perinatal morbidity and mortality after diagnosis (e.g. use of corticosteroids)

23. 23 Option in next pregnancy if unsuccessful history indicated cerclage: Transabdominal cerclage Hydroxyprogesterone caproate 250 mg IM weekly from 16 to 36 weeks

24. 24

25. 25

26. Other Measures to Reduce Preterm Labor S moking cessation T reatment of drug misuse T reatment of asymptomatic bacteriuria M aintenance of a normal body mass index Avoiding an interpregnancy interval of less than six months, and ideally less than 12 months Prevention and reduction of multifetal gestations (like single embryo transfer in ART) Low-dose aspirin, not recommended for preterm labor for moderate or high risk factors but preeclampsia reduce risk for the disorder and its sequelae (PTL) No single biomarker performs well as a screening test for predicting sPTB in asymptomatic low risk women 26

27. Arrest Preterm Labor: Goals of Treatment Delay delivery by at least 48 hours (when safe to do so) so that antenatal corticosteroids (primary or rescue) administered for maximal fetal/neonatal effects Provide time for safe transport of the mother Prolong pregnancy (when safe to do so) when conditions such as pyelonephritis or abdominal surgery, are present but unlikely to cause recurrent preterm labor Treatment can be discontinued after these goals have been achieved

28. Tocolytic Agents (<34 weeks) Cyclooxygenase inhibitors: Indomethacin ( 1 st line in 24 to 32 weeks ) Calcium channel blockers: Nifedipine ( 1 st line in 32 to 34 weeks , 2 nd line in 24 to 32 weeks) Beta-agonists: Ritodrine and Terbutaline (2 nd line in 32 to 34 weeks) Oxytocin receptor antagonists: Atosiban Magnesium sulfate

29. Most Recent Evidence 2009 Meta-analysis of placebo controlled trials: Tocolytics are superior to placebo (75 to 93% Vs 53%) in inhibiting contractions 2012 meta-analysis of 75 RCTs declared the same 50 percent not treated with tocolytics did not delivered in the short term or even preterm No significant perinatal outcomes improvement In a 2014 meta-analysis of 33 randomized trials comparing magnesium sulfate  with no treatment/placebo: No statistical reduction in birth <48 hours (not less or more effective than other tocolytic options)

30. Drugs MOA Dose S/E Indomethacin COX inhibitor 50-100 mg (loading) followed by 25 mg every 4 to 6 hours Reflux, gastritis, bleeding, oligohydramnios, constriction of ductus arteriosus CCB ( nifedipine ) Blocks the entry of calcium inside cell 10-20mg every 3-6 hours(oral) Hypotension, headache, nausea Magnesium sul fate Competitive inhibition of calcium ions Loading dose 4-6 g IV over 20 minutes followed by infusion of 1-2gm/hour for 12 hours Relatively safe Flushing, perspiration, muscle weakness Betamimetics Activation of intracellular enzyme( adenylate cyclase, cAMP) reduces intracellular free calcium Ritodrine: IV 50ug/min and increased by 50ug in every 10 minute till contraction cease and infusion cont. for 12 hours after that Terbutaline : subcutaneous, 0.25 mg every 3-4 hours Headache, palpitation, hypotension, cardiac arrest, hypokalemia Oxytocin antagonist ( Atosiban ) Blocks myometrial oxytocin receptors 300ug/min IV Nausea, vomiting, chest pain (rare) Nitric oxide ( GTN) Smooth muscle relaxant Patches Headache 30

31. 31

32. Short-Term Tocolytic T herapy

33. Maternal Corticosteroid T herapy Advocated where the pregnancy is <34 weeks for fetal lung maturation Betamethasone 12 mg IM 24 hours apart for two doses Dexamethasone 6 mg IM every 12 hours for four doses Reduce neonatal RDS, IVH, NEC Risks of antenatal corticosteroid use : Premature rupture of the membranes Insulin-dependent DM Transient reduction of fetal breathing and body movements

34. What about Tocolysis in 34 to 37 weeks? Somewhat controversial Consensus: Tocolysis should not be used to delay delivery for completion of a course of steroids at this gestational age

35. Management of Labor To prevent birth asphyxia and development of RDS To prevent birth trauma First stage Second stage The patient is put to bed to prevent early rupture of the membranes The birth should be gentle and slow To ensure adequate fetal oxygenation by giving oxygen to the mother by mask Episiotomy Epidural analgesia is of choice Tendency to delay is curtailed by low forceps Labor should be carefully monitored preferable with continuous EPM The cord is to be clamped immediately at birth to prevent hypervolemia and hyperbilirubinemia Cesarean delivery (HTN, abruption or malpresentation ) Shift the baby to NICU NICU is absolutely essential for good outcome

36. Treatment does not necessarily PREVENT preterm labor.

37. Preterm Neonate C are I mmediate management following birth: The cord is to be clamped quickly The cord length is kept long (about 10-12 cm) The air passage should be cleared of mucus promptly and gently using a mucus sucker Adequate oxygenation (not exceeding 35%) The baby should be wrapped including head in a sterile warm towel (36.5˚-37.5˚C) Aqueous solution of vitamin K 1 mg IM

38. Summary of Management

39. Evidence based Guidelines after Resolution of Acute Episode of Preterm Labor Steroid for patients at 23 +0 to 33 +6 weeks of gestation If receiving progesterone, continue the same regimen but do not start the therapy Can be managed in OPD basis provided fetal well being is ensured and no other obstetric/medical complications Complete bed rest is not recommended but avoid work if working more than 40 hours per week, night shifts, prolonged standing, or heavy physical work

40. Evidence based Guidelines after Resolution of Acute Episode of Preterm Labor Avoid sexual activity if experience an increased frequency or intensity of contractions after sexual intercourse Travel in car, train, or airline travel doesn't significantly increase the risk of PTL or preterm birth unless other contraindications are evident Maintenance tocolysis , antibiotic prophylaxis, home uterine monitoring, and fibronectin testing do not improve outcomes after an episode of arrested PTL Neither a benefit nor serious harm from use of a cervical pessary has been established. Only utilizing pessaries in this setting in a clinical trial Bedrest, hydration, and sedation  — There is no convincing evidence that bedrest, hydration, or sedation is effective for prevention or treatment of preterm labor. Furthermore , extended and hospitalized bedrest increase the risk of thromboembolic events.

41. Follow up visit after delivery Assessment is done for infants general health, weight, hydration and degree of jaundice Breastfeeding technique Immunization schedule Multivitamins, oral supplements Any new problem need to identified Pattern of feeding, its adequacy are explored

42. References Williams obstetrics 25 th edition, Y. Spong and Jodi S. Dashe Obstetrics by Ten Teachers, 20 th edition, Louise Kenny,  Jenny E. Myers Lockwood Charles et al . Preterm labor: Clinical findings, diagnostic evaluation, and initial treatment, https:// www.uptodate.com/contents/preterm-labor-clinical-findings-diagnostic-evaluation-and-initial-treatment S. Hyagriv et al. Inhibition of acute preterm labor, https:// www.uptodate.com/contents/inhibition-of-acute-preterm-labor R. Julian et al. Preterm birth: Risk factors, interventions for risk reduction, and maternal prognosis, https:// www.uptodate.com/contents/preterm-birth-risk-factors-interventions-for-risk-reduction-and-maternal-prognosis C. Steve et al. Management of pregnancy after resolution of an episode of acute idiopathic preterm labor, https:// www.uptodate.com/contents/management-of-pregnancy-after-resolution-of-an-episode-of-acute-idiopathic-preterm-labor D.C . Dutta’s Textbook of Obstetrics, 9 th Edition

43. Thank you