Workshop Diagnosis management Threatened Pre Term Birth

Da Nang hospital Obstetrics& Gynecology department Wo rks ho p Diag no s is & manag e me nt Thre ate ne d Pre Te rm Birth Prepare by Phan Tin Da Nang, 6/2009 DEFINITION Preterm labour The onset of labour (regular uterine contraction and effacement and dilatation of cervix) after the gestation of viability and before 37 completed weeks of pregnancy • 3-7% of pregnancies • 85% of neonatal deaths due to prematurity • 10% of survivors suffer long term handicap Diagnosis of threatened preterm birth Symptomatic women  Aymptomatic women c prior cone biopsy, mullerian anomalies, multiple D&C  Asymptomatic women once short cervical length – prior preterm birth – cervical length < 25 mm Diagnosis of threatened preterm birth Asymptomatic women : • PPROM? Asymptomatic women subclinical: • Fibronectin • CERVICAL EXAMS • Vaginal exams • Ultrasound: Transvaginal cervical length assessment Compendium on Preterm Birth Pathophysiologic Pathways to Preterm Birth Produced in cooperation with: American Academy of Pediatrics The American College of Obstetricians and Gynecologists Association of Women’s Health, Obstetric and Neonatal Nurses Pathways to Preterm Birth Activation of Maternal-Fetal HPA Axis • Maternal-Fetal Stress • Premature Onset of Physiologic Initiators Inflammation • Infection: - Chorion-Decidual - Systemic Pathological Uterine Distention Abruption • Multifetal Pregnancy • Polyhydramnios • Uterine Abnormality Thrombin Thrombin Rc Ils, Fas L TNF CRH E1-E3 Decidual Hemorrhage Chorion Decidua + proteases Gap jct PG synthase Oxt recep + Mechanical Stretch CRH uterotonins PPROM Cervical Change PTD Uterine Contractions Source: Lockwood CL Unpublished data, 2002 Pathways to Preterm Birth • Inflammation  Infection - ~40% • Activation of the maternal-fetal hypothalamic– pituitary–adrenal (HPA) Axis  Stress - ~30% • Decidual hemorrhage  Abruption - ~20% • Uterine distension  Stretching - ~10% Sources: Lockwood CJ, Iams JD Preterm labor and delivery In: Precis: Obstetrics, 3rd ed ACOG, 2005; Lockwood CJ, Kuczynski E Paediatr Perinat Epidemiol 2001;15:78-89 Inflammation Amniochorionic-decidual systemic inflammation IL-6 CRH TNF/IL-1 + FasL + + Uterotonins (PG, endothelin) contractions cervical change Proteases/apoptosis rupture of membranes Source: Lockwood CJ, Kuczynski E Markers of risk for preterm delivery J Perinat Med 1999;27:5-20 Copyright 1999 by Walter de Gruyter and Company Reproduced with permission of Walter de Gruyter and Company via Copyright Clearance Center HPA Axis Activation: The Role of CRH Maternal/Fetal HPA Axis glucocorticoid + placental/membrane/decidual CRH PGs contractions cervical change CRH-BP + rupture of membranes Source: Lockwood CJ, Kuczynski E Markers of risk for preterm delivery J Perinat Med 1999;27:5-20 Copyright 1999 by Walter de Gruyter and Company Reproduced with permission of Walter de Gruyter and Company via Copyright Clearance Center HPA Axis Activation: The Role of Estrogens & Cortisol Early onset physiologic initiators UPV abnormality Activation of Fetal HPA Axis ACTH Adrenal + cortisol DHEA/16-OH DHEA Placenta, Decidua Fetal Membrane CRH + + PG contractions Placenta ? membranes E1-E3 Myometrial oxytocin receptors, gap jct, MLCK calmodulin, PG synthase cervical change rupture of membranes Source: Lockwood CJ, Kuczynski E Markers of risk for preterm delivery J Perinat Med 1999;27:5-20 Copyright 1999 by Walter de Gruyter and Company Reproduced with permission of Walter de Gruyter and Company via Copyright Clearance Center Nifedipine Dosage 20mg orally stat followed by 20mg orally after 30 minutes if contractions persist followed by 20mg orally after 30 minutes if contractions persist followed by 20mg orally tds for 48 – 72 hours if indicated Note: Maximum dose is 120mg per day After 72 hours if maintenance therapy is required, patients can be changed over to the long acting nifedipine (Adalat OROS ®)30 – 60 mg orally per day Nifedipine Note: Nifedipine tablets should be chewed then swallowed to enable faster absorption Nifedipine Side Effects Hypotension: In normotensive patients the effects of Nifedipine on blood pressure are minimal Care must be exercised in hypertensive patients, where blood pressure changes may be significant If significant hypotension occurs, treatment should be discontinued IV rehydration with Normal Saline or Hartmann’s may be considered Tachycardia, palpitations, Flushing, Headaches, dizziness, Nausea Nifedipine Observations Continuous CTG while contracting QID temperatures ½ hourly pulse and blood pressure for the first four hours, then 2nd hourly pulse and blood pressure for the first 24 hours, then QID observations Oxytocin receptor antagonists for inhibiting preterm labour A range of tocolytic agents have been used to inhibit preterm labour and postpone preterm birth These are effective in delaying delivery for up to 48 hours Magnesium sulphate as a tocolytic agent is ineffective in delaying or preventing preterm birth and is associated with increased infant mortality A recent review suggested that oxytocin antagonists could be effective and safe in preterm labour (Coomarasamy 2002) This systematic review examines the role of oxytocin receptor antagonists in the management of women in preterm labour to assist clinicians and women in informed decision making Atosiban compared with placebo When compared with placebo, atosiban resulted in lower birthweight (weighted mean difference -138.31 gm 95% confidence interval (CI) -248.76 to -27.86, two trials 692 infants); an increase in infant deaths at 12 months of age (relative risk (RR) 6.15; 95% CI 1.39 to 27.22, one trial of 583 infants); and an increase in maternal adverse drug reaction (RR 4.02; 95% CI 2.05 to 7.85, two trials of 613 women) Atosiban compared with betamimetics More atosiban exposed infants had birthweights under 1500 gm than infants exposed to betamimetics (RR 1.96; 95% CI 1.15 to 3.35, trials of 575 infants) However, neither neonatal mortality nor measures of neonatal morbidity differed Atosiban was associated with a significant reduction in maternal drug reactions requiring cessation of treatment (RR 0.04; 95% CI 0.02 to 0.11, trials and 1034 women) Authors' conclusions Implications for practice The results of this review not support the superiority of atosiban over betamimetics or placebo in terms of tocolytic efficacy or infant outcomes, although atosiban has a clear advantage over betamimetics with respect to maternal sideeffects profile The higher incidence of infant deaths seen in one trial where atosiban was compared with placebo merits caution Maintenance therapy with oxytocin antagonists for inhibiting preterm birth after threatened preterm labour Compared with placebo the use of atosiban as maintenance therapy for prevention of recurrent preterm labour did not reduce the incidence of preterm birth before 37 weeks (RR 0.89; 95% CI 0.71 to 1.12), 32 weeks (RR 0.85; 95% CI 0.47 to 1.55), or 28 weeks (RR 0.75; 95% CI 0.28 to 2.01) While not defined as an a priori outcome measure of this review, the median interval from the start of maintenance therapy to the first recurrence of labour was prolonged (32.6 days in the atosiban group vs 27.6 days in the placebo group, P=0.02), as was the time to recurrence of preterm labour (36.2 vs 28.2 days, P=0.03) The number of women who received 'rescue' tocolytic treatment was not significantly reduced Authors' conclusions Implications for practice The available evidence does not support the use of oxytocin receptor antagonists for maintenance therapy after a period of preterm labour Prophylactic antibiotics for inhibiting preterm labour with intact membranes The contribution of subclinical genital tract infection to the aetiology of preterm birth is gaining increasing recognition, but the role of prophylactic antibiotic treatment in the management of preterm labour is uncertain Since rupture of the membranes is an important factor in the progression of preterm labour, it is important to see if the routine administration of antibiotics confers any benefit, prior to membrane rupture Prophylactic antibiotics for inhibiting preterm labour with intact membranes Main results This review has been updated (2002) to include data from the 'ORACLE II 2001' trial (six times larger than the previous 10 trials combined), which now dominates the results of this review Meta-analysis of the 11 included trials (7428 women enrolled) shows a reduction in maternal infection with the use of prophylactic antibiotics (relative risk 0.74, 95% confidence interval 0.64 to 0.87) but fails to demonstrate a benefit or harm for any of the prespecified neonatal outcomes Prophylactic antibiotics for inhibiting preterm labour with intact membranes Implications for practice Prophylactic antibiotics cannot be recommended in the routine management of women in preterm labour with intact membranes There is increasing awareness that subclinical infection plays a role in the aetiology of preterm labour, it is certainly not the only pathway leading to preterm labour For this reason it is not possible that all women (and/or their babies) in preterm labour with intact membranes could benefit from antibiotic treatment Co rtic o s te ro ids • Effectively reduce the risk of: – Hyaline membrane disease – Necrotising enterocolitis – Intracranial haemorrhage – Death and disability • Are safe in the short and long term • Must be given within 24 hrs and days • Repeat once if [...]... 25 operations to prevent 1 preterm birth MANAGEMENT • Stopping contractions has been the focus of therapeutic approaches • Maintenance therapy after threatened preterm labor for preventing preterm birth • Therapy should consider maternal & neonatal outcomes • Prophylactic Antibiotics ? • Lung maturity be achieved • Where to deliver ? • How to deliver ? Traditional Approaches to Preterm Labor Management... Reassure mother Discard fFN swab • • Ongoing uterine activity Clinical suspicion of preterm labour Treat for preterm labour Discard fFN swab Send fFN swab Positive • • Treat for preterm labour - Tocolytics - Corticosteroids - Antibiotics Consider transfer to appropriate level of care BCRCP (2005) Obstetric Guideline 2A – Preterm Labour, p 11 Negative • • • • Reassure mother F/U endovaginal ultrasound of... distension – Myometrial stretch Source: Lockwood CJ, Iams JD In: Precis: Obstetrics, 3rd ed ACOG, 2005 Common Final Pathway to Preterm Birth • Increase in uterotonins – Prostaglandins – Endothelin – Oxytocin • Increase in protease expression – – – – Matrix metalloproteinases (MMP-1 and MMP-9) Plasminogen activator Plasmin Elastase Preterm Birth How do we identify who is at Risk? Risk Factors Fetal Fibronectin... & Prediction of preterm labor • True cervical length: 25-50 mm at 14-30 wks • Cannot measure CL before 14 weeks – Internal cervical os is indistinguishable from LUS • Shortening starts at internal os after 14 wks • Funneling