Preterm Labour and Premature Rupture of Membranes
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    Preterm Labour and Premature Rupture of Membranes Preterm Labour and Premature Rupture of Membranes Presentation Transcript

    • 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
    • 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.
    • 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
    • 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.
    • 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 Unpublished data, 2002.
    • 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.
      • 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
      • Uterine anomalies
        • Cervical incompetence
        • Malformation of uterus
      • Foetal
        • Multiple pregnancy
        • PROM
        • Hydramnions
        • Congenital fetal malformation
      • Idiopathic
    • 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
      • 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
    • How do we identify who is at Risk? Preterm Birth Risk Factors Cervical Length Fetal Fibronectin Symptoms of PTL
      • 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
      • 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
      • 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%.
    • 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 )
      • 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
      • 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
      • 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
      • 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.
    •  
      • Infection
        • Ureoplasma
        • Gonorrhoea
        • Chlamydia
        • Syphilis
        • Untreated UTI
      • 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
      • 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
      • 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
      • 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
    • Prevention/Intervention Strategies Tocolytics Education Targeting High Risk Women Bedrest Home Uterine Monitoring Frequent Digital Exam Hydration Population Based strategies
      • 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
      • Secondary prevention
      • 1.cerclage
      • 2.antibiotics
      • 3.tocolysis
      • 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
      • 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
      • 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
      • 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)
      • 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
      • 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
      • 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
      • 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)
      • 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
      • 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
      • 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
      • 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
      • Antiprostaglandin drugs
        • inhibit prostaglandin synthetase or cyclooxygenase (COX)
        • PG facilitate entry of calcium into cell, enhance development of gap junctions
      • 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
      • 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
      • 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
      • 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
      • 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
      • 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
      • Complications
      • Maternal infection
      • Abruptio
      • Prematurity
      • Fetal distress, cord compression
      • Deformation and contractures
      • Pulmonary hypoplasia
      • Fetal infection
      • Management
      • Diagnosis
        • Speculum examination
        • Nitrazine test
        • Ferning,
        • Ultrasound
        •  -fetoprotein, FFN
      • Gestational age
      • Presence of labour
      • Infection
      • Maternal infection
      • Fever, uterine tenderness, fetal or maternal tachycardia, foul smelling, vaginal discharge, leukocytosis, uterine contractions
      • For queries mail me at
      • [email_address]
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    • Thank you