Preterm Labour and Premature Rupture of Membranes

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  • 1. Preterm Labour and Premature Rupture of Membranes
    • Date : 17.04.2009
    • Dr. Pradeep Kumar Garg
    • Assistant Professor
    • Department of Obstetrics and Gynaecology
    • All India Institute of Medical Sciences
    • New Delhi
    • Email:pkgarg_in2004@yahoo.com
  • 2. Preterm Labour (PTL)
    • Definition
    • WHO : Regular contractions associated with cervical changes
      • <37->20 weeks of pregnancy
    • Incidence - 8-10%
      • 60% of all neonatal mortality
    • Threatened PTL - presence of uterine contractions in absence of cervical changes.
  • 3. Definitions
    • Preterm (or premature) infant
      • Infant born before 37 completed weeks of gestation
    • Moderately preterm infant
      • Infant born between 32 and 36 completed weeks of gestation
    • Very preterm infant
      • Infant born before 32 completed weeks of gestation
  • 4. Magnitude of the Problem
    • The infant mortality rate for very preterm infants (delivered < 32 weeks of gestation) is nearly 75 times the rate for infants born at term
    • 20% all infants born <32 weeks do not survive the first year of life
    • Preterm birth is directly responsible for 75–90% of all neonatal deaths that are caused by lethal congenital malformations.
  • 5. Pathways to Preterm labour proteases PT L Uterine Contractions Cervical Change • Infection: - Chorion-Decidual - Systemic Decidual Hemorrhage CRH E1-E3 Thrombin Thrombin Rc Pathological Uterine Distention • Multifetal Pregnancy • Polyhydramnios • Uterine Abnormality Inflammation • Maternal-Fetal Stress • Premature Onset of Physiologic Initiators Activation of Maternal-Fetal HPA Axis CRH + Chorion Decidua uterotonins Mechanical Stretch Gap jct PG synthase Oxt recep PPROM Ils, Fas L TNF + Abruption Source: Lockwood CL. Unpublished data, 2002.
  • 6. History of previous preterm birth Primary risk for a preterm delivery in multiparas is a history of previous preterm birth (relative risk [RR] 2.62) Mercer BM,Am J Obstet Gynecol. 1999;181:1261–1221 Evaluation of the literature shows that history of a previous preterm delivery is consistently the most important risk factor for subsequent preterm birth.
  • 7.
    • Causes
    • Maternal
      • Fever
      • Acute pyelonephritis
      • Acute appendicitis
      • Abdominal operation
    • Chronic disease
      • Hypertension, nephritis, diabetes, severe anemia, decompensated heart disease
    • Pregnancy complications
      • Pregnancy induced hypertension
      • Antepartum hemorrhage
  • 8.
    • Uterine anomalies
      • Cervical incompetence
      • Malformation of uterus
    • Foetal
      • Multiple pregnancy
      • PROM
      • Hydramnions
      • Congenital fetal malformation
    • Idiopathic
  • 9. INFECTION …
    • ASCENDING INTRAUTERINE INFECTION IS CONSIDERED TO HAVE FOUR STAGES
    • The first stage : change in the vaginal/cervical microbial flora or the presence of pathologic
    • organisms
    • Second stage : deciduitis .
    • Third stage ( choriovasculitis ) or ( amnionitis )
    • Fourth stage : Once in the amniotic cavity, the bacteria may gain access to the fetus by different ports of entry
    R Goldenberg NEJM 2000
  • 10.
    • Risk Factors
    • Non white race
    • Previous preterm delivery
    • Low body mass index
    • Extremes of ages (<17 and >35)
    • Strenous work stress
    • Tobacco use
    • Hemoglobin < 10 g
    • Bactereuria
    • Low socioeconomic status
  • 11. How do we identify who is at Risk? Preterm Birth Risk Factors Cervical Length Fetal Fibronectin Symptoms of PTL
  • 12.
    • THE PAPIERNIK-BERKHAUER(1969)SCORING MATRIX
    • MODIFIED BY GONIK –CREASY (1980-1986)
    0-5:low risk 5-9 :medium risk ≥ 10 :high risk points Socio economic factors Previous medical history Daily habits Current pregnancy 1 2 children at home; low s.e status 1 abortion <1 yr since last birth Works outside Unusual fatigue 2 Age<20/>40 yr Single parent 2 abortions Smoke>10 cig/day >3 flights of stairs without elevator Gain<5 kg by 32 wk Albuminuria,bacteriuria,hypertension 3 V low s.e status Ht<150 Wt<45 kg 3 abortions Heavy/stressful work Long daily commuting Extensive travelling breech@32 wks Head engaged @32 wks Febrile illness 4 Age<18 yrs pyelonephritis Bleeding after 12wk Short cervix Open int os Uterine irritabily 5 Uterine anomaly T2 abortion Des Exp Cone bx Placenta praevia hydramnios 10 Ptb,repeated t2 abortion Twins Abdominal surgery
  • 13.
    • Signs / Symptoms
    • Persistent contractions (painful or painless) associated with cervical changes
    • Intermittent abdominal cramping, pelvic pressure or backache
    • Increase in vaginal discharge
    • Vaginal spotting or bleeding
  • 14.
    • Biological markers for predicting PTL
    • Fetal fibronectin
      • Glycoprotein produced by the chorion
      • Normally present in cervical secretion in early gestation and just before term labor
      • Presence after >24 weeks is a marker for the disruption of the chorioamnion and underlying decidua due to inflammation with or without infection
      • If test is negative < 1% will deliver in next week or two and test is positive then risk of PTD on next week or two is 20%.
  • 15. Fetal fibronectin (cont)
    • False positive : bleeding, ruptured membranes and digital cervical exam
    • False negative : lubricant soap
    • Screenigof asymptomatc women at low risk is not recommended
    • Useful in women when;
      • Symptom occurs between 24-34 weeks
      • Membranes are intact and cervical dilatation is <3 cm
      • For short term prediction ( 7-14 days )
  • 16.
    • Biological markers for predicting PTL (contd…)
    • Salivary estriol
      • Maternal levels of serum estradiol and salivary estriol increases before onset of term and PTL
      • A cut off > 2. 1ng/dl yielded a sensitivity of 40%, specificity of 93%
      • Levels infuenced
        • Diurnal pattern (lowest during day , highest in night
        • Corticosteroids suppresses estriol value
  • 17.
    • CRH
      • Source placenta and fetal membranes; highest in T3.
      • RR 3.3 at 33 weeks
    •  hcg and  FP
    • Increased levels associated with PTL, abnormal placentation, disruption of choriodecidual integrity
    • Relaxin
  • 18.
    • Cervical length (CL)
    • Risk of PTD increases if CL is 30mm or less at 24 weeks,
    • Manual examination
      • subjective, interobserver variability 52%
      • internal os not measurable
    • Transvaginal USG vs digital examination
      • TVS can detect shortening of Cx canal earlier
      • no significant inoculation with bacteria
      • minimal discomfort
      • 99% agreed for similar procedure
  • 19.
    • TransaAdominal USG of Cx is inadequate
    • 1.fetal can obscure the Cx especially after 20 weeks
    • 2.requires UB filling which can elongate Cx and mask funneling
    • 3.visualization not clear due to long distance
    • TransLabial/Transperineal USG is more useful
    • 1.fetal parts don’t obscure vision
    • 2.bladder filling not required
    • 3.no pressure exerted on cervix
    • 4.additional transducer not required
    • 5.well accepted
    • Drawback:gas in rectum can hamper vision specially ext os.
    • Difficult to master.
  • 20.  
  • 21.
    • Infection
      • Ureoplasma
      • Gonorrhoea
      • Chlamydia
      • Syphilis
      • Untreated UTI
  • 22.
    • Bacterial vaginosis
      • Bacterial vaginosis is an alteration of the normal vaginal flora, reduction in lactobacilli with increase in gram negative and anaerobic bacteria (G. vaginalies, bacteroides, mobiluncus, peptostreptococcus, mycoplasma
      • 3 of 4 criteria should be present
    • Diagnosis
      • Vaginal pH > 4.5,Amine odour with 10% KOH, Clue cells on wet mount, Homogenous vaginal discharge
  • 23.
    • Bacterial vaginosis:
      • two fold risk of PTB
      • Cochrane meta-analysis : no reduction by routine screening and treatment.But those with history of PTB benefited.
      • screen pts with history of PTB. treat with oral metronidazole for 7 days (vaginal treatment had no effect) .
      • vaginal clindamycin for 3 days or oral 5 day course also effective
  • 24.
    • Multiple pregnancy
    • PTL occurs in 50% of twins
    • 76% triplets
    • 90% quadruplets
    • Those with preterm contractions but without cervical changes do not require tocolytics.
    • Those in preterm labor : tocolysis + steroids
    • Greater risk of pulmonary edema with tocolytics
  • 25.
    • Treatment of PTL
    • WHY?
      • To prevent complication of prematurity
      • e.g.
        • Respiratory distress syndrome (RDS)
        • Intraventricular haemorrhage (IVH)
        • Bronchopulmonary dysplasia (BPD)
        • Patent ductus arteriosus (PDA)
        • Necrotizing enterocolitis (NEC)
        • Retinopathy of prematurity (ROP)
        • Sepsis
  • 26. Prevention/Intervention Strategies Tocolytics Education Targeting High Risk Women Bedrest Home Uterine Monitoring Frequent Digital Exam Hydration Population Based strategies
  • 27.
    • Prevention of PTB
    • Primary Prevention
    • 1.improve quality of life and nutritional status
    • 2.reduction in physical and emotional stress. bed rest.
    • 3.education programs for signs and symptoms, contractions, pelvic pressure, vaginal discharge
    • 4.hydration
    • 5.progesterone
    • 6.antioxidants and omega-3 fatty acids : uncertain
    • 7.cerclage
    • 8.diagnosis & treatment of infections
    • 9.role of ART
    • 10.twins and high order multiples
  • 28.
    • Secondary prevention
    • 1.cerclage
    • 2.antibiotics
    • 3.tocolysis
  • 29.
    • Prophylactic therapy like bed rest, hydration and sedation in asymptomatic women at increased risk for preterm delivery has not been demonstrated to be effective.
    • ACOG practice bulletin 2003, Cochrane review 2003
    • Stop smoking and substance abuse and reduce heavy work load
    • Role of ART : reduce rate of multiple pregnancies, single embryo transfer
  • 30.
    • Progesterone therapy to prevent PTL
      • decrease in myometrial progesterone receptor with PTL and term labor.
      • antinflammatory response,
      • immunosuppression : suppresses cytokine pathways thus preventing rejection of fetus in utero.
      • 17 alpha hydroxyprogesterone caproate weekly I.m.to women at high risk for PTL results in lower rates of PTB
  • 31.
    • Cervical Cerclage
    • RCOG study concluded that 96% of elective cerclages were unnecessary,with no perinatal improvement .
    • In a post-hoc analysis those with three or more pregnancy losses seemed to have improved outcome
    • Recommendations
      • high risk patients can be followed by serial Cervical USG
      • TVS during 2 nd trimester.
      • Except:anatomic defect at or near internal os,
      • 3 or more losses,
      • inability to follow with TVS
  • 32.
    • Cervical cerclage cont.
      • high risk patients screened 1 to 4 weekly between 16 and 24 weeks
    • Elective transabdominal cerclage
      • lacerations upto LUS,
      • cervical surgical amputation
      • Cx Length < or =2.5 at 24 weeks (10 th percentile) is the critical threshold for increased risk for PTB)
  • 33.
    • Cervical cerclage cont.
    • Adjuntive treatment
      • Antibiotics: multiple urogenital cultures should be obtained . Short course of antibiotics before cerclage placement or as empiric medical therapy can be considered, but no evidence to support it. Long-term antibiotics avoided (increases resistance)
      • Tocolytics: short-term indomethacin anti-inflammatory properties and tocolytic, but no data to support empiric use. Absence of anti-inflammatory properties of beta blocker, nifedipine, Mg sulphate precludes there use
      • Corticosteroids: not used before 24 weeks
  • 34.
    • Cerclage in Multifetal pregnancy : no evidence to support use of elective, urgent, emergent cerclage
    • After delivery:
      • if during pregnancy urogenital infection documented then evaluation for subclinical gynecologic infection indicated.
      • Anatomical evaluation using HSG,hysteroscopy, MRI, TVS
  • 35.
    • Infection and preterm birth
      • 50% of PTB associated with ascending genital tract infection eg. intrauterine, lower genital tract infection, distant infection like periodontitis
      • polymicrobial ureaplasma urealyticum, Mycoplasma hominis, anaerobes, group B streptococci, Gardenella vaginalis, E. coli, peptostreptococci, Bacteroides
  • 36.
    • Treatment of infections
      • antibiotics should not be given routinely in PTL with intact membranes for prolonging pregnancy
      • definitely diagnosed intra-amniotic infection either by clinical criteria (fever, uterine tenderness, maternal or fetal tachycardia) or by amniocentesis, give i.v. antibiotics and deliver regardless of gestation
    • Consider amniocentesis if
      • any signs and symptoms of chorioamnionitis
      • early gestation <28 wks
      • failure of tocolysis (eg. before a second tocolytic)
  • 37.
    • Tocolytics in PRL
    • 1. beta agonist
    • 2. magnesium sulphate
    • 3. antiprostaglandins
    • 4. calcium channel antagonists
    • 5. oxytocin antagonists
    • 6. nitric oxide donors
    Goals 1. allow administration of corticosteroids 2. allow time for transfer to tertiary care 3. during maternal antenatal surgeries 4. uterine relaxation during ECV
  • 38.
    • Betamimetic
    • MOA : b2 activator
    • Terbutaline 0.25mg s/c every 20 min to 3 hrs
    • Ritodrine : start at 50-100 mg/min, increase 50µg/ every 10min, max 350µg
    • CI : cardiac disease, poorly controlled diabetes and thyroid disease
    • Mat S/E : arrhythmias, pulmonary edema, hypotension, tachycardia, hyperglycemia, hypokalemia
    • Fetal S/E : Tachycardia, hyperglycemia, myocardial and septal hypertrophy
    • Neonatal : tachycardia, hypoglycemia, hypocal, hyperbil, IVH
  • 39.
    • Magnesium sulphate
    • MOA : calcium antagonist;
      • Inhibits calcium refluxat cell membrane, competes for binding sites
      • Increased intracellular c AMP which further decreases calcium.
    • Dose : 4-6gm bolus IV for 20 min then 2-3g/hr
    • CI : myasthenia gravis, impaired renal function
    • Mat S/E : flushing, lethargy, headache
    • Muscle weakness, pulmonary edema, cardiac arrest
    • Fetal S/E : lethargy, hypotonia, respi depression
  • 40.
    • Calcium channel blockers
    • Blocking Voltage dependent L-type calcium channels in smooth muscles; nifedipine and ritodrin.
    • Dose : 30mg loading dose, then 10-20mg 4-6 hr
    • CI : cardiac, renal disease, maternal hypotension, concomitant use with magnesium sulphate
    • Mat S/E : flushing, headache, dizziness
    • Transient hypotension
    • Fetal S/E none
  • 41.
    • Antiprostaglandin drugs
      • inhibit prostaglandin synthetase or cyclooxygenase (COX)
      • PG facilitate entry of calcium into cell, enhance development of gap junctions
  • 42.
    • Prostaglandin synthetase inhibitors
    • Indomethacin 50mg rectally or 50-100 mg orally, 25-50mg every 6 hr for 48 hrs
    • CI : sig hepatic or renal disease, peptic ulcer disease, coagulation disorder, thrombocytopenia, sensitivity
    • Mat S/E : nausea, heartburn
    • Fetal S/E : constriction of DA, pulmonary hypertension, reversible decrease in renal function, hyperbil, NEC, IVH
  • 43.
    • Summary
    • Although tocolytics may prolong pregnancy they don’t improve perinatal outcomes, but do have adverse maternal effect
    • As a rule they should be given with corticosteroids
    • Most do not recommend use of tocolytics >= 34 weeks POG
    • No role of maintenance tocolysis
  • 44.
    • Antenatal corticosteroids
    • All fetuses between 24 – 34 wks POG at risk of preterm delivery should be considered
    • Decision should not be altered by race, gender, availability of surfactant replacement therapy
    • Those eligible for tocolysis are eligible for corticosteroids
    • Optimal benefit begins 24 hrs after initiation
    • Significant decrease in incidence and severity of RDS, IVH, NEC
  • 45.
    • Until data establish a favorable benefit-to-risk ratio,repeat courses of steroids including rescue therapy should be reserved for patients enrolled in clinical trials. Multiple courses lead to worse outcome or no benefit
    • Long-term FU of infants given single course show no adverse effects
    • Betamethasone and dexamethasone
    • Readily cross placenta
    • Have long half lives
    • Limited mineralocoticoid activity
    • Similar efficacy in decreasing RDS ( 51% vs 44%)
    • Betamethasone is more effective in reducing IVH, PVL than dexamethasone so betamethasone is a better choice
  • 46.
    • Conduct of Delivery
    • Tertiary care centre, specialized staff
    • Cesarean delivery to obviate trauma from labor and vaginal delivery has not been validated
    • CS did not lower risk of mortality or ICH in <1500 gm
    • Episiotomy may be necessary in absence of relaxed vagina outlet
    • No use of routine forceps
    • Cesarean section for preterm breech
  • 47.
    • Preterm Premature Rupture of Membranes
    • Risk factors
      • SES
      • Smoking
      • Vaginal bleeding x 2-7
      • Short cervix
      • Prior cervical surgery
      • Vitamin C, copper and zinc deficiency
      • Multifetal pregnancy
      • Previous history of PTB or PPROM
      • Pre-existing medical illness
      • Genital tract infection, BV, chlamydia, mycoplasma
  • 48.
    • Complications
    • Maternal infection
    • Abruptio
    • Prematurity
    • Fetal distress, cord compression
    • Deformation and contractures
    • Pulmonary hypoplasia
    • Fetal infection
  • 49.
    • Management
    • Diagnosis
      • Speculum examination
      • Nitrazine test
      • Ferning,
      • Ultrasound
      •  -fetoprotein, FFN
    • Gestational age
    • Presence of labour
    • Infection
  • 50.
    • Maternal infection
    • Fever, uterine tenderness, fetal or maternal tachycardia, foul smelling, vaginal discharge, leukocytosis, uterine contractions
  • 51.
    • For queries mail me at
    • [email_address]
  • 52.
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  • 53. Thank you