Preterm Labor 2021 Update
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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.
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Preterm Labor 2021 Update
- 1. PRETERM LABOR PRESENTED BY: Dr. Aryan (Anish Dhakal) 5TH MARCH, 2021
- 2. Introduction Labor starts before the 37th 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
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- 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 A. Clinical predictors a. Multiple pregnancy b. History of prior preterm birth c. Presence of genital tract infection d. Symptoms of Preterm Labor B. Biophysical predictors a. Uterine contraction b. Bishop score (≥4) c. Cervical length C. Biochemical predictors a. Fetal fibronectin in cervicovaginal discharge b. Others IL-6,8; TNFα c. 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.
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- 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
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- 26. Other Measures to Reduce Preterm Labor Smoking cessation Treatment of drug misuse Treatment of asymptomatic bacteriuria Maintenance 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 (1st line in 24 to 32 weeks) Calcium channel blockers: Nifedipine (1st line in 32 to 34 weeks, 2nd line in 24 to 32 weeks) Beta-agonists: Ritodrine and Terbutaline (2nd 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 sulfate 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
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- 32. Short-Term Tocolytic Therapy • Maternal: uncontrolled DM, thyrotoxicosis, severe HTN, placenta previa or abruption, severe preeclampsia or eclampsia, cervical dilatation >4 cm, contraindication to tocolytic drug • Fetal: fetal distress, fetal death, congenital malformation and pregnancy beyond 34 weeks • Obstetric: rupture of membranes, chorioamnionitis, medical COI Contraindication:
- 33. Maternal Corticosteroid Therapy 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 Care Immediate 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
- 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 25th edition, Y. Spong and Jodi S. Dashe Obstetrics by Ten Teachers, 20th 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, 9th Edition
Notas do Editor
- Short cervix a risk factor for microbial invasion of amniotic cavity
- Hemorrhage into the decidua (abruption) generates thrombin, which binds to PARs to activate the ERK1/2 MAP kinase signaling cascade, which directly inhibits PR expression in decidual cells and activates COX-2 to increase PGF-2alpha production. The latter contributes to ERK1/2-mediated inhibition of PR expression, which triggers contractions and directly promotes increased MMP-3 activity, causing a proteolytic cascade that degrades fetal membranes to promote PROM, and induces cervical change. Decidual inflammation associated with ascending genital tract infections with or without chorioamnionitis generates IL-1beta, which binds to its receptor to also activate the ERK1/2 MAP kinase signaling cascade inhibiting decidual cell PR expression. In addition, IL-1beta activates COX-2 and releases MMPs via the NF-kappaB signaling pathway. Premature maturation of the fetal HPA axis or maternal or fetal stress causes increased circulating cortisol (glucocorticoid), which binds to its receptor to increase levels of the immunophilin co-chaperone protein, FKBP51. Increased FKBP51 binds to both the GR and PR to decrease their transcriptional activity (functional progesterone withdrawal). Thus, ultimately COX-2 is activated and MMP-3 released to promote PTB. HPA: hypothalamus-pituitary-adrenal; PAR: protease-activated receptors; IL: interleukin; ERK: extracellular signal-regulated kinase; MAP: mitogen-activated protein; NF-kappaB: nuclear factor-kappa-light-chain-enhancer of activated B cells; COX-2: cyclooxygenase 2; FKBP51: FK506-binding protein 51; PGF-2alpha: prostaglandin F2-alpha; PR: progesterone receptor; MMP: matrix metalloproteinase; PTB: preterm birth; PROM: premature rupture of membranes; GR: glucocorticoid receptor.
- We make the diagnosis of preterm labor based upon clinical criteria of regular painful uterine contractions accompanied by cervical change (dilation and/or effacement). Vaginal bleeding and/or ruptured membranes in this setting increase diagnostic certainty [33]. Because the clinical findings of early labor are poorly predictive of the diagnosis, over-diagnosis is common until labor is well established.
- TVS=Transvaginal sonography Fibronectin=glycoprotein that binds fetal membrane to decidua Bishop Score-=Cervical dilation, Cervical effacement, Cervical consistency, Cervical position, Fetal station
- The contraction criteria are those used for selecting subjects in research settings. Before the use of ultrasound for measuring cervical length, research studies also required documented cervical change or cervical effacement ≥80 percent or cervical dilation >2 cm. These criteria were chosen because women who did not meet them were often ultimately diagnosed with false labor and went on to have a late preterm or term delivery [34]. Preterm contractions may have same criteria but no progressive cervical dilatation and cervical changes For twin pregnancies <34 weeks and cervical dilation <3 cm, transvaginal ultrasound measurement of cervical length and laboratory analysis of cervicovaginal fFN level help to support or exclude the diagnosis of preterm labor: •Cervical length >35 mm and no cervical change on digital examination after a four- to six-hour period of observation – Low risk for preterm delivery: discharge. •Cervical length <25 mm – High risk of preterm delivery: initiate interventions to reduce morbidity associated with preterm birth. •Cervical length 25 to 35 mm – fFN testing. If positive, initiate interventions to reduce morbidity associated with preterm birth. If negative, discharge after a 6- to 12-hour period of observation.
- Prior PTB is the strongest risk factor for future PTB, and recurrences often occur at the same gestational age. The frequency of recurrent PTB is 15 to 30 percent after one PTB and up to 60 percent after two PTBs.
- Like fFN, placental alpha-microglobulin-1 (PAMG-1) [28-30] or phosphorylated insulin-like growth factor binding protein-1 (pIGFBP-1) [31] in vaginal or cervical secretions suggests disruption of the fetal membranes (ROM or labor) and are potential markers of an increased risk of preterm birth. However, the utility of these tests has not been validated in either large or randomized clinical trials.
- Bedrest, hydration, and sedation — There is no convincing evidence that bedrest, hydration, or sedation is effective for prevention or treatment of preterm labor [113-115]. Furthermore, extended and hospitalized bedrest increase the risk of thromboembolic events
- Progesterone supplementation appears to reduce the risk of PTB by approximately 30 percent in women with a singleton pregnancy and a history of sPTB.
- Before 32 weeks, fetal echocardiographic evaluation is useful for monitoring ductal effects if the duration of indomethacin therapy exceeds 48 hours.
- n a practice bulletin, the American College of Obstetricians and Gynecologists (ACOG) opined: "Interventions to reduce the likelihood of delivery should be reserved for women with preterm labor at a gestational age at which a delay in delivery will provide benefit to the newborn. Because tocolytic therapy is generally effective for up to 48 hours, only women with fetuses that would benefit from a 48 hour delay in delivery should receive tocolytic treatment" [5]. Inhibition of acute preterm labor is less likely to be successful as labor advances to the point that cervical dilation is greater than 3 cm. Tocolysis can still be effective in these cases, especially when the goal is to administer antenatal corticosteroids or safely transport the mother to a tertiary care center Predelivery administration of magnesium sulfate is neuroprotective for the neonate. The minimum duration of administration that results in neuroprotection is not known but is less than 24 hours.
- Contraindications to use of specific drugs are reviewed below in the discussions of specific tocolytics.
- Administration of an initial course of antenatal corticosteroids at 34+0 to 36+6 weeks of gestation is somewhat controversial; however, there is consensus that tocolysis should not be used to delay delivery for completion of a course of steroids at this gestational age.
- The lack of benefit from antibiotics may be because the subclinical infectious process leading to preterm labor may be too advanced for treatment to be effective by the time preterm labor is clinically apparent. It is also possible that once the inflammatory cascade has been triggered, it will continue to amplify whether or not the inciting infection is treated. However, clinicians should be cautious before concluding there are no benefits from antibiotic therapy of preterm labor. Theoretically, a subgroup of women who have subclinical intrauterine infection may benefit from treatment with antibiotics, as demonstrated in a primate model and we cannot startifty tehm beforehand Failure of metronidazole to prevent preterm delivery
- Administration of an initial course of antenatal corticosteroids at 34+0 to 36+6 weeks of gestation is somewhat controversial; however, there is consensus that tocolysis should not be used to delay delivery for completion of a course of steroids at this gestational age.