Post on 12-Apr-2017
Preterm Labour
Dr Max Mongelli
Western Clinical School University of Sydney
Nepean Hospital
http://drmaxmongelli.weebly.com
Definitions
Threatened pre-term labour Pre-term labour Pre-term delivery
Incidence
Approx 5-6% in Australia More than 10% in the USA Second leading cause of mortality
congenital anomaliesafter
Risk Factors (1)
Stress Occupational fatigue Smoking/substance abuse Poor antenatal care
Risk Factors (2)
Excessive or impaired uterine Multiple pregnancy Polyhydramnios Fibroids Uterine anomaly
distension:
Risk Factors (3)
Cervical factors: History of second trimester loss Cervical surgery Premature cervical dilatation or
effacement
Risk Factors (4)
Infections: Systemic infections STD's Pyelonephritis Bacteriuria Periodontal disease
Risk Factors (5)
Fetal & placental factors:
Congenital anomalies IUGR Abruption Vaginal bleeding Placenta previa
Causes of Preterm Labour
Major focus of O & G research. 80% spontaneous onset
50% PTL 30% PPROM
20% due to to intervention for maternal or fetal indications
Four Major Categories
Activation of hypothalamic/pituitary/adrenal maternal or fetal
Inflammation Decidual hemorrhage Uterine over-distention
axis:
Activation of HPA Axis
Maternal physical/emotional stress Placental vasculopathy Increased Increased Increased
secretion
secretion secretion
of CRH – fetal ACTHplacental estrogenof placental PG's
Activation of myometrium
Inflammation
Both systemic and genital tract infections Chorioamnionitis in 50% of preterm labours
before 30 weeks' gestation Can occur with intact membranes Raised cytokines (interleukins, TNF, GSF) Enhanced prostaglandin production
Bacteria
Some organisms have a direct role in PTLindependent of inflammatory mediators
Psudomonas, staph, strep, bacteroides,enterobacter produce proteases that can breakdown fetal membranes
Can also produce phospholipase A2 andendotoxins, stimulating uterine contractions
Bacteria
Increased rates of PTL noted in womenGBS, chlamydia and syphilis
with
Risk of PTL reduced by treating: Asymptomatic bacteriuria Gonorrhea BV in high risk patients for PTL
Oral Bacteria
Increased rates of PTL noted in women withperiodontal disease
? intrauterine infection following “descent”from
Case from
oral cavityreport: Bergeyella bacterium isolated both the mouth and amniotic fluid of
patient with intact membranes having PTL at24 weeks
Decidual hemorrhage
Vaginal bleeding in more than one trimesterincreases risk of PTL 7-fold
Placental histopathology: occult decidualhemorrhage noted in 36-38% of cases of PTB
PPROM may be related to high concentrationstissue factor
of
Decidual hemorrhage
Decidual TF combines with FVIIa to activateFX, to generate thrombin
Thrombin is a potent inducer of IL8, causing localised inflammatory reactions.
Leads to degradation of fetal membrane extracellular matrix, PPROM
Uterine Over-distention
Up-regulation of oxytocin receptors Formation of gap junctions PGE2 and PGF Myosin light chain kinase
Uterine Over-distention
Polyhydramnios Multiple pregnancy
Cervical Incompetence
In most cases a secondary Cervical cone biopsy LLETZ, laser cone Increased risk of PTL -
< 37 weeks: OR 3.4 <32 weeks: OR 4.6 <28 weeks: OR 12.4
effect
Prevention of PretermLabour
Potentially effective interventions
Progesterone supplements Smoking cessation Avoidance of drugs & alcohol Reduce rate of multiple pregnancy Cervical cerclage Reduce occupational stress Nutrition Early diagnosis & treatment of infection
Progesterone supplements
Most trials use 17-alpha-hydroxyprogesteronecaproate, weekly IMIReduction in PTL rates by 15-70%Most effective in women with previous PTL at<34 weeksIncreased risk of GDM (OR 2.9)ACOG recommends use in women with previousPTL onlyNo reduction in perinatal mortalityMore research needed
Stop smoking
Cigarette smoking has a dose-dependentrelationship with preterm labour
Partially due to smoking-related complications Cessation of smoking likely to be beneficial, but
not proven in RCT’s
Avoidance of drugs and alcohol
Cocaine Alcohol ? Cannabis
Reduction in multiple pregnancies
Multiple pregnancies six times more likely todeliver preterm
Risk increases with increasing no. of fetuses Valid indication before starting ART Limit no. of embryos transferrred
Cervical Cerclage
Cervical incompetence based on historyultrasound findings
RCOG study of 1292 women
or
Significant reduction in preterm births<33weeks
NNT = 25 cerclages Increased risk of puerperal infection Increased risk of PTL in twins
Reduction of Work Fatigue
Excessive physical demandsincreased risk (OR 1.63)
Working > 42 hrs/week Standing > 6 hrs/day Low job satisfaction No RCT’s available
related to
Nutritional interventions
No fish consumption linked to excess risk ofPTL
Fish high
(OR 19.6)oil supplements: one multi-centre RCT in risk women showed a significant
reduction in PTL (OR 0.54) Trial with docosahexanoic acid supplements:
significant prolongation of pregnancy CARRDIP trial: marked reduction in risk of
preterm labour (1/141 vs 11/149)
Early detection and treatment ofinfection
Asymptomatic bacteriuria: treatment significantlyreduces risk of PTL or LBW infants (OR 0.60)
Chlamydia, gonorrhea, BV: routine screening notindicated
Women with previous PTL and +ve for BV may benefit from treatment
Trichomonas: treatment of asymptomatic women may increase risk of PTL
Case Scenario 1
19 yo G3P1M1 late booking at 22 weeks Previous preterm delivery at 29 weeks Heavy smoker, nil alcohol Works in supermarket as check-out
assistant, prolonged standing Offensive vaginal discharge
Case Scenario 2
35 yo G5P1M3 booking at 9 weeks Previous preterm delivery at 27 weeks
to placental abruption Three first trimester miscarriages Family history of thromboembolism
due
Diagnosis of Preterm Labor
No universally accepted definition Regular uterine contractions and Cervical dilatation or effacement
Tests for PredictionDelivery
Cervico-vaginal fibronectin
Ultrasound measurement of cervical length
of Preterm
Treatment of Preterm Labor
No generally accepted criteria forstarting tocolysis
About 30-50% of threatened preterm labours spontaneously resolve
Treat the underlying cause if possible
General Measures
No proven benefits for:
Bed rest Hydration Sedation
Objectives of Tocolysis
Delay delivery so that steroids may begiven
Allow safe transport of the mother if possible
Prolong pregnancy when there are self- limiting causes of labour e.g. sepsis
Contraindications to Tocolysis
APH with hemodynamic instability Severe pre-eclampsia/eclampsia Chorioamnionitis Severe IUGR Evidence of fetal compromise Lethal fetal anomaly Fetal demise
Benefits of AntenatalReduce risk of: RDS (RR 0.66) NEC (RR 0.46) IVH (RR 0.54) Severe bruising
Steroids
Systemic infection(RR 0.56)
in the first 48 hr of life
Admission to NICU (RR 0.80) Neonatal mortality (RR 0.69)
Antenatal Steroids
Effective in women with SROM Maximum effect at 48 hrs
and PET
Betamethasone 11.4 mg IM 12 hrs apart Beneficial effects wear off after 2 weeks No significant maternal side effects
TOCOLYTIC AGENTS
Betamimetic agents Nifedipine NSAIDS Atosiban Magnesium sulphate
BETA-ADRENERGIC RECEPTOR AGONISTS
BETA-ADRENERGIC RECEPTOR AGONISTS
Mechanism of action:
Cause myometrial relaxation by bindingwith beta-2 receptors and increasing intracellular adenyl cyclase.
Drop in intracellular calcium Target cells eventually become desensitized to the effect of beta-adrenergic agonists (tachyphylaxis).
BETA-ADRENERGIC RECEPTOREFFICACY
AGONISTS:
Meta-analyses:
Reduction in no. of births within0.63).
48 hrs (RR
No decrease in no. of births within 7 days No change in perinatal mortality Marginal decrease in RDS cases
BETA-ADRENERGIC RECEPTOR AGONISTS:MATERNAL SIDE EFFECTS
Tachycardia Palpitations Lowered blood pressure SOB Myocardial ischemia Pulmonary oedema (0.3%) Hyperglycemia, hypokalemia
BETA-ADRENERGIC RECEPTOR AGONISTS:FETAL SIDE EFFECTS
Tachycardia Neonatal hypoglycemia
TERBUTALINE:DOSAGE
Continuous iv infusion (2.5 mcg/min increased to max. of 25 mcg/min)
S.C.I. 25 mg stat Stop if HR>120 or symptomatic Monitor K+ and BSL
CALCIUM CHANNEL BLOCKERS
Block the influx of Ca+ through the cell membrane
Reduction of intracellular free calcium Inhibition of myosin light chain kinase
phosphorylation Relaxation of uterine muscle
EFFICACY OF NIFEDIPINE
Meta-analysis of 12 RCT’s:
Reduction in no. of births within 7 days (RR 0.76) Reduction in no. of births before 34 weeks (RR 0.83) Lower risk of RDS (RR 0.63), NEC (RR 0.23), IVH
(RR 0.59), jaundice (RR 0.73) Fewer maternal side effects (RR 0.14)
NIFEDIPINE :MATERNAL SIDE EFFECTS
Peripheral vasodilator:
Nausea, flushing, headache Palpitations Reduction in MAP, reflex tachycardia Rarely severe hypotension
NIFEDIPINE :FETAL SIDE
EFFECTS
Animal studies: reduced uterineumbilical blood flow
and
No evidence of toxicity in humans
NIFEDIPINE :CONTRAINDICAT
IONS
Known allergy LV dysfunction or cardiac failure Hepatic dysfunction Concomitant use of magnesium:
respiratory paralysis
NIFEDIPINEDOSAGE
:
Half-life 2-3 hrs, single dose 20 mg po stat
lasts up to 6 hrs
Repeat 30 mins later if still contracting Maintenance 20-40 mg qid Max dose 160 mg in 24 hrs
ROUTINE ANTIBIOTICS IN PRETERMLABOUR WITH INTACT MEMBRANES
Results of ORACLE and meta-analysis:
No improvement in neonatal outcomes Reduction in maternal infection (RR 0.74) Uncertainty about optimal antibiotics and
regime
MANAGEMENT FOLLOWING SUCCESSFULTOCOLYSIS
Optimal approach unknown – limited data
Prolonged hospitalisation probably Bed rest not proven effective Avoid physically demanding work
of no value
MANAGEMENT FOLLOWING TOCOLYSIS:SEXUAL ACTIVITY
Observational data only Higher mortality amongst infected
associated with recent coitus: 11%infants vs 2.4%
Increased rates or RDS, jaundice, low Apgar scores (x 2)
Effect stronger among preterm births Prudent to suggest avoidance of coitus after
successful tocolysis
MANAGEMENT FOLLOWING TOCOLYSIS:MAINTENANCE TOCOLYSIS
Most RCT’s are small Endogenous prostaglandins may increase
oxytocin receptor density Cochrane review of maintenance oral beta-
agonists: no significant benefits May be useful for temporary relief of
painful contractions
MANAGEMENT FOLLOWING TOCOLYSIS:REPEATED COURSES OF ANTENATAL
STEROIDS
Repeat courses of steroids improve neonatal pulmonary outcomes, especially in earlier gestational ages
Evidence of delayed neuronal maturation and increased risk of IUGR in animal studies
Humans: reduced birth weight only with 4 or more courses
Catch-up growth by time of discharge from hospital
MANAGEMENT FOLLOWING TOCOLYSIS:REPEATED COURSES OF ANTENATAL
STEROIDS
Long-term neuro-developmental data not available
Optimal number of courses of steroids unknown
Two courses probably safe
MANAGEMENT FOLLOWING TOCOLYSIS:RISK OF IUGR
Threatened PTL may be an indication of fetal stress arising from unfavourable intrauterine environment.
Placental pathology: increased incidence of fetal or maternal vascular lesions without inflammation
Risk of giving birth to SGA infant (OR 2.2) Need closer surveillance with USS for growth
and Doppler studies
CASE SCENARIO 3
33 y.o weeks
G1P0 presents to rural hospital at 31
Strong, painful contractions for 3 hours Slight brownish PV loss Normal recordings; cephlic presentation CTG “irritable uterus” pattern Cervix 2 cm long os closed How would you manage?
CASE SCENARIO 4
21 y.o G2P1 at 29 weeks recently dischargedfrom hospital following TPL successfully stopped with nifedipine
Completed course of steroids Single mother, smokes 20/day How would you manage her?