Subject:PTL Dr shakeri

Preterm labor Important cause of perinatal mortality & morbidity 50 % of all major neurologic handicaps

Increased in survival Use of C.S Regionalization prenatal care Improved method of mechanical ventilation Use of surfactant Improved nutritional therapy

Mechanism of labor onset Hormonal (progestron withdrawal) Oxytocin Prostaglandins Cytokines IL.1-IL.6-TNF ( stimulate the amnion and decidua to produce PG) B-TGF ( inhibit PG production) Other factors endothelin nitric oxide (NOS)

Infection as a cause of preterm labor Linked with symtomatic nongenital infection Subclinical Infection an important cause of PTL a- Histologic chorioamnionitis increased b- recognized infections in mother and neonates c- sepsis and meningitis are increased 3 to 10 fold d- positive culture of amniotic fluid/membrane/decidua 3-24% (<32 week)

e. Biochemical markers of infection often present f e. Biochemical markers of infection often present f. Bacteria or their products induce PTL in animal

Biochemical marker Amniotic fluid glucose <14 mg/dl Serum WBC CRP Amniotic or serum cytokines (IL.6 most sensitive marker)

Ureaplasma urealyticum ,chlamyclia trachomatis ,GBS in the lower genital tract is not associated with PTL T.vaginalis is associated with PTL bacterial vaginosis (anaerobe) PTL X 2-3 Untreated bacteriuria ,PTL X 2

Route of upper genital tract infection Ascending through the vagina and cervix Hematogenously (placenta-bacteremia from periodontal disease) Contamination during amniocentesis or cvs Spread from Abd cavity via the fallopian tubes

Important points Among women in PTL with intact membranes mycoplasma,anaerobic organism and gardnerella Vaginalis are most commonly found in amniotic fluid N.Gonorrhoeae and c.trachomatis are rarely found Ecoli and GBS occasionally found

Use of antibiotic to prevent PTL in women with PTL and PROM With intact membrane .GBS prophylaxis is indicated .don’t give AB routinely to prevent PTL With PROM .at 24-32 week ampicillin + erythromycin for 7 days or erythromycin for 10 days

Epidemiology Incidence 12% Preterm delivery .PTL 50% .PROM 33% .cervical incompetence

Major preterm labor risk factor Prior preterm birth *6-8 Multiple gestations *6-8 African american race *3.3 Low socioeconomic status *2-2.6

Minor risk factor of PTL Modifiable risk .poor maternal weight gain .physically demanding work .smoking .anemia .bacteriuria .bacterial vaginosis .maternal systemic infection (pyelonephritis)

Nonmodifiable risk .extremes of age <17 - >40 .prior multiple abortion .history of uterin abnormality .short status .low pregnancy weight

Prediction of woman at risk for PTL Receive c.s prior to delivery If necessary ,receive tocolytic Transported to level 3 perinatal center

Criteria for screening tests Sensitivity ↑ Specificity Negative predictive value ↑ Positive predictive value Ascertainment of early, asymptomatic disease Early treatment alter health outcome Disease is important ,prevalent

Acceptable to population Diagnosis / treatment available Simple , reliable , valid Cost proportional to benefit Risk scoring systems contraction monitoring-HUAM Screening for B.V Sal-est Cervical evaluation

Fetal fibronectin presence 20-34 w strongly associated with PTL Sensitivity is low –Specificity is high Used to women with intact membrane, cervical dilation less than 3 cm ,GA 24-34 w results should be available within 24h False positive (recent intercourse-vaginal examination presence of B.V -vaginal bleeding) >50 ng → positive test

All of these tests fail to meet the goals of an ideal screening test

Preterm labor defined uterin contractions >4 contractions per 20 minutes Cervical dilation 2cm or more in N..P 3cm or more in M.P Cervical effacement > 80% Uterin contraction and cervical change

treatment Hormonal treatment Alcohol treatment Bmimetics Mgso4 Antiprostaglandin agents Oxytocin analogs Ca channel blockers

Absolute CI of tocolytic theraphy Severe preeclampsia Severe abruptio Severe bleeding Frank chorioamnionitis Fetal death Fetal anomaly incompatible with live Severe FGR Mature lung Maternal cardiac arrythmia

Relative CI to tocolytic therapy Mild chronic hypertension Mild abruptio Stable previa Maternal cardiac disease Hyper thyroidism Uncontrolled diabetes Fetal distress Fetal anomaly Mild IUGR Cervix dilatation greater than 4 cm

B - adrenergic agonists The most wildly prescribed Ritodrined and terbutaline (SC-IV) Disadvantage - side effect(none of them are completely B2 selective ( Negative B2 effect Maternal hypotension Decreased u.o.p increased glucose secretion Hypokalemia Pulmonary edema

Negative B1 effect Tachycardia Palpitation Constipation Decreased gastric emptying Hypokalemia Agitation jilleriness

Severe maternal adverse effect Cardiac arrhythmia Myocardial infraction Pulmonary edema Postpartum cardiomyopathy death

Fetal effect Tachycardia Increased C.O.P Redistribution of blood flow Increased thickness of inter ventricular septum Neonatal supra ventricular tachycardia Myocardial ischemia and necrosis hydrops Hypoglycemia Intra ventricular hemorrhage

Are B-mimetics efficacious?

Magnesium sulfate In recent years, tocolytic of choice in many delivery units Protocol of administration The blood levels of 6-8mg/dl are optimal for tocolysis

Maternal side effect Common (flushing-sense of warmth-headache nystagmus-nausea-dizziness-lethargy) Serious (pulmonary edema-neuromuscular blockage- osteopenia-respiratory depression-cardiac arrest)

Neonatal side effect Respiratory depession Decreased beat to beat variability Decreased muscle tone Drowsiness Depression Poor respiratory effort Low apgar score

Is mgso4 ?efficacious

Ca channel blocker Mechanism Protocol of Ad Maternal side effect Decrease in mean arterial pressure Symptomatic hypotension Nausea-headache-facial flushing

Neonatal side effect Well tolerated by the fetus Neonatal heart block Growth restriction , acidosis , stillbirth No protocol established the safety of using these medication together

Prostaglandin synthesis inhibitors Mechanism Protocol of Ad Fetal CI Growth restriction Renal anomaly Oligohydramnios Chorioamnionitis Ductal dependant cardiac lesion Twin to twin transfusion syndrom

Maternal CI Renal and hepatic D Active peptic ulcer Poorly control H.T Asthma in aspirin-sensitive patients Coagulation disorder Maternal side effect GI upset and hemorrhage Alteration in coagulation Thrombocytopenia Renal injury(prolonged treatment)

Neonatal side effect Constriction of ductus arteriosus Neonatal PHT 5-10% Oligohydraminous increased ADH direct effect on renal blood flow Necrotizing enterocolitis Intraventricular hemorrhage

Effective agent that is well tolerated by mother and fetus Indomethacin to be comparable to ritodrine and MgSo4 Exposure should be limited to 48 hrs and G.A less than 32 weeks

Other tocolytic agents Atosiban (analog oxytocin) Nitroglycerin Cyclo-oxygenase inhibitor Progestin Nitroxide inhibitor

Maintenance tocolysis following arrest of PTL Oral tocolysis with B-mimetic Continous subcutaneous administration of terbutalin Oral MgSO4 Oral nifedipine Long-term tocolysis with prostaglandin synthetases inhibitors is contraindicated

در حال حاضر کارایی هیچ کدام از درمانها به عنوان Maintenance tocolytic agent تایید نشده است و همه آنها با عوارض قابل توجه همراه بوده.

Ancillary therapy for women in PTL Antibiotic therapy Antibiotic therapy in PTL with intact membrane is not indicated GBS prophylaxis should be administered Hydration therapy Bed rest C.S (all women at risk for PTL prior to 34 weeks receive C.S

Key points The rate of PTL is increasing in the united states. fFN and vaginal ultrasound of cervix and promising technologies to identify women at risk for preterm delivery. Screening for B.V and T.Vaginal is not indicated. Management of women with asymptomatic shortening of the cervix controversial Tocolytic therapy has not been associated with improvements in neonatal outcome. Weekly courses of antenatal C.S should not be routinely prescribed. Antenatal progesteron therapy may reduce the risk of preterm birth (PTB) and low birth weight (LBW) in women with previous PTB