Management of Late-Preterm Premature Rupture of Membranes : The PPROMEXIL-2 Trial
Preterm Labour and Premature Rupture of Membranes
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Transcript of Preterm Labour and Premature Rupture of Membranes
Preterm Labour and
Premature Rupture of Membranes
Date : 17.04.2009
Dr. Pradeep Kumar GargAssistant Professor
Department of Obstetrics and GynaecologyAll India Institute of Medical Sciences
New DelhiEmail:[email protected]
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.
DefinitionsPreterm (or premature) infant
Infant born before 37 completed weeks of gestation
Moderately preterm infantInfant born between 32 and 36 completed weeks of gestation
Very preterm infantInfant 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 lifePreterm birth is directly responsible for 75–90% of all neonatal deaths that are caused by lethal congenital malformations.
Pathways to Preterm labour
Source: Lockwood CL. Unpublished data, 2002.
proteases
PT LUterine
ContractionsCervical Change
• Infection: - Chorion-Decidual - Systemic
DecidualHemorrhage
CRHE1-E3
ThrombinThrombin Rc
Pathological UterineDistention
• Multifetal Pregnancy• Polyhydramnios• Uterine Abnormality
Inflammation
• Maternal-Fetal Stress
• Premature Onset of Physiologic Initiators
Activation of Maternal-Fetal
HPA Axis
CRH+
ChorionDecidua
uterotonins
Mechanical StretchGap jctPG synthaseOxt recep
PPROM
Ils, Fas LTNF
+
Abruption
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.
CausesMaternal
FeverAcute pyelonephritisAcute appendicitisAbdominal operation
Chronic diseaseHypertension, nephritis, diabetes, severe anemia, decompensated heart disease
Pregnancy complicationsPregnancy induced hypertensionAntepartum 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 STAGESThe 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?
Risk Factors
CervicalLength
FetalFibronectin
Symptomsof PTL
Preterm Birth
THE PAPIERNIK-BERKHAUER(1969)SCORING MATRIXMODIFIED BY GONIK –CREASY (1980-1986)
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 yrSingle parent
2 abortions Smoke>10 cig/day>3 flights of stairs without elevator
Gain<5 kg by 32 wkAlbuminuria,bacteriuria,hypertension
3 V low s.e statusHt<150Wt<45 kg
3 abortions Heavy/stressful workLong daily commutingExtensive travelling
breech@32 wksHead engaged @32 wksFebrile illness
4 Age<18 yrs pyelonephritis Bleeding after 12wkShort cervixOpen int osUterine irritabily
5 Uterine anomalyT2 abortionDesExpCone bx
Placenta praeviahydramnios
10 Ptb,repeated t2 abortion
TwinsAbdominal surgery
0-5:low risk5-9 :medium risk ≥10 :high risk
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 examFalse negative : lubricant soapScreenigof asymptomatc women at low risk is not recommendedUseful in women when;
Symptom occurs between 24-34 weeksMembranes are intact and cervical dilatation is <3 cmFor 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 inadequate1.fetal can obscure the Cx especially after 20 weeks2.requires UB filling which can elongate Cx and mask funneling3.visualization not clear due to long distance
TransLabial/Transperineal USG is more useful1.fetal parts don’t obscure vision2.bladder filling not required3.no pressure exerted on cervix4.additional transducer not required5.well acceptedDrawback: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 PTBCochrane 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
Tocolytics
EducationTargetingHigh RiskWomen
Bedrest
HomeUterineMonitoring
FrequentDigitalExam
Hydration
PopulationBased
strategies
Prevention/Intervention Strategies
Prevention of PTBPrimary Prevention
1.improve quality of life and nutritional status2.reduction in physical and emotional stress. bed rest. 3.education programs for signs and symptoms, contractions, pelvic pressure, vaginal discharge4.hydration 5.progesterone6.antioxidants and omega-3 fatty acids : uncertain7.cerclage8.diagnosis & treatment of infections9.role of ART10.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 CerclageRCOG 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 outcomeRecommendations
high risk patients can be followed by serial Cervical USGTVS during 2nd 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 (10th
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 useCorticosteroids: 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
BetamimeticMOA : b2 activatorTerbutaline 0.25mg s/c every 20 min to 3 hrsRitodrine : start at 50-100 mg/min, increase 50µg/ every 10min, max 350µgCI : cardiac disease, poorly controlled diabetes and thyroid diseaseMat S/E : arrhythmias, pulmonary edema, hypotension, tachycardia, hyperglycemia, hypokalemiaFetal S/E : Tachycardia, hyperglycemia, myocardial and septal hypertrophyNeonatal : 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 benefitLong-term FU of infants given single course show no adverse effects
Betamethasone and dexamethasone Readily cross placentaHave long half lives Limited mineralocoticoid activitySimilar 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 MembranesRisk factors
SESSmokingVaginal bleeding x 2-7Short cervixPrior cervical surgeryVitamin C, copper and zinc deficiencyMultifetal pregnancyPrevious history of PTB or PPROMPre-existing medical illnessGenital 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
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