2. Preterm Labor Abdullah H. Baghaffar

3. Preterm labor is defined as the presence of uterine contractions of sufficient frequency and intensity to effect progressive effacement and dilation of the cervix prior to term gestation (bet. 20 and 37 wk). Definition:

4. 8-12% of all deliveries Accounts for 85% of all perinatal morbidity and mortality. Epidemiology:

5. Four potential pathways leading to preterm delivery have been identified: 1.Stress, eg: IUGR 2.Stretch, eg: Multiple pregnancy 3.Infection, eg: Chorioamnionitis 4.Hemorrhage, eg: Placental abruption Pathophysiology:

6. StressStretchHemorrhageInfection Maternal – Fetal Stress Premature Onset of Physiologic Initiators

7. Etiology:

8. Risk factors for preterm birthRelative risk Intra-amniotic infection Multiple gestation Placental abruption Third-trimester vaginal bleeding Second-trimester vaginal bleeding Prior preterm birth Uterine anomalies DES Exposure Urinary tract infection Smoking(>10 cigarettes\day) Illicit drug use Maternal age>35 year Low socioeconomic status 50 40 35 10 2 2-5 5-7 4 2 2-3 2 Risk Factors:

9. Although risk factors for preterm birth have been identified, reliance on risk factors alone will fail to identify over 50% of pregnancies that deliver preterm. Serial normal cervical evaluation is reassuring. However abnormal findings are associated preterm delivery in only 4% of low-risk and 20% of high-risk patients. Prediction of Preterm Birth

10. A number of biochemical markers have been associated with preterm delivery, but only cervicovaginal fetal fibronectin (fFN) has been established as a screening tool. The value of fFN lies in its negative predictive value:99% of women with a negative fFN at 22-34 weeks will still be pregnant in 7 days. Prediction of Preterm Birth

11. A number of endocrine assays are also being developed to predict preterm labor. Elevated maternal salivary estriol (>2.1ng/ml) is predictive of preterm delivery in high-risk populations. Other endocrine assays (relaxin, corticotropin-releasing hormone) are being developed. Prediction of Preterm Birth

12. Diagnosis of Preterm Labor: A firm diagnosis of preterm labor is necessary before treatment is considered. Diagnosis requires: 1.Uterine contractions lasting at least 30 seconds. 2.At least two contractions in a 10-minute period. 3.Persistence of contraction pattern for at least 30 minutes 4.Cervix >2 cm dilated or 80% effaced or documented change in the cervix.

13. Goals of management of preterm labor include: 1.Early identification of risk factors 2.Timely diagnosis 3.Identifying the etiology 4.Evaluating fetal well being. 5.Providing prophylactic pharmacologic therapy to prolong gestation and reduce the incidence of RDS and IAI. 6.Initiating tocolytic therapy when indicated. 7.Establishing a plan of maternal and fetal surveillance with patient/provider Management

14. A.Initial Transfer to appropriate facility if stable Hydration (NS at 150ml/hr) Bed rest in L&D Sedation Avoid repeated pelvic exams U/S examination of fetus Prophylactic antibiotics, controversial but may help delay delivery, important to consider if PPROM Management

15. B.Suppression of Labor-Tocolysis Does not inhibit preterm labor completely, but gives time to allow Dexamethasone use/ tranfer to appropriate center. Requirements –all must be satisfied Preterm labor Live, immature fetus Intact membranes Cervical dilatation of <4 cm Absence of maternal or fetal contraindications Management

16. Contraindications to Tocolysis: Maternal Bleeding (placenta previa or abruption), maternal disease (hypertension, diabetes, heart disease), pre-eclampsia or eclampsia, chorioamnionitis, PPROM (relative). Fetal Erythroblastosis fetalis, severe congenital anomalies, fetal distress/demise, IUGR, multiple gestation (relative). Management

17. –Tocolytic procedure Ensure availability of necessary personnel and equipment to assess mother and fetus during labor and care for baby of the predicted GA if therapy fails If no contraindications present, agent used depends on clinical situation Management

18. Tocolytic agentRoute of administration(do se) EfficacyMajor maternal side-effects Major fetal side- effects Calcium channel blockers.nifedipine Oral(20-30 mg q3- 4 hrs) EffectiveHypotention,reflex tachycardia, headache, nausea, flushing, potentiates cardiac depressive effect of magnesium sulfate - β adrenergic agonists.terbutaline sulfate.ritodrine hydrochloride -i.v.(2 μ g/min infusion, max 80mcg/min) -SC (0.25 mgq20 min) -Oral maintinance(2.5-5 mgq4-6hrs) -i.v. pump(0.02 ml/h) -i.v. (50mg/min infusion, max 350mg/min) -i.m(5-10 mg q2-4h) -oral maintenance(10- 20 mg q3-4h) Effective Not effective Effective Not effective Jitterness, anxiety,reslessness, rash, nausea, vomiting, cardiac dysrythmia, chest pain,MI, palpitations, hypotension, tachycardia,, pulmonary edema, paralytic ileus, hypokalemia, hyperglycemia, acidosis Fetal tachycardia, hypotension, ileus, hyperinsulinemia, hypoglycemia, hypocalcemia

19. Tocolytic agentRoute of administration(do se) EfficacyMajor maternal side-effects Major fetal side- effects Oxytocin antagonist.atosiban i.v. (1 μ M/min infusion,max32 μ M/min EffectiveNausea, headache, chest pain, arthralgia Prostaglandin inhibitors.indomethacin -oral (25-50mg q 4- 6hrs) -rectal (100 mg q 12hrs) Effective GI effects(nausea, heart burn), headache, rash, interstitial nephritis, increased bleeding time Transient oligurea, oligohydramnios, premature closure of ductus artteriosus and persistent pulmonary hypertension, IVH Magnesium sulfate-i.v. (4-6 g bolus,2- 3g/h infusion -oral maintinance Effective Not effective Nausea, vomiting, ileus, headache, weakness, hypotension, pulmonary edema, cardiorespiratory arrest Deacreased fetal heart rate variability, neonatal drowziness, hypotonia Others.nitroglycer in -TD(10-50 mg q day) -i.v. (100 μ g bolus, then1-10 μ g/kg/min) Unproven Hypotension,headach e Fetal tachycardia

20. C.Enhancement of fetal pulmonary maturity Betamethasone valerate 12 mg IM q24h x 2 or Dexamethasone 6 mg IM q12h x 4 28-34 weeks GA: reduces incidence of RDS 24-28 weeks GA: reduces severity of RDS, overall mortality rate of IVH Specific maternal contraindications: active TB, viral keratosis, maternal DM Management

21. Delivery of Preterm Infant A certain number of patients will not respond to tocolytic therapy With modern neonatal care, the lower limit of potential viability is 24 weeks or 500 g Continuous fetal heart monitoring is extremely important With a vertex presentation, vaginal delivery is preffered

22. Delivery of the Preterm Infant Use of outlet forceps and an episiotomy to shorten the second stage are advocated About 23% of infants present as a breech at 28 weeks, compared with 4% at term This carries an increased risk for cord prolapse or compression For the breech fetus estimatedat less than 1500g,neonatal outcome is improved by cesarean birth

23. Prematurity is the leading cause of perinatal mortality and morbidity. 30 weeks or 1500 g= 90% survival 33 weeks or 2000 g=99% survival Morbidity due to asphyxia(may lead to cereberal hemorrhage), hypoxia(may lead to necrotizing enterocolitis), sepsis, RDS, IVH, thermal instability, retinopathy of prematurity and bronchopulmonary dysplasia. Prognosis

24. Currently there are no agents approved to arrest preterm labor Preventative measures include: good prenatal care, identifing pregnancies at risk, treat silent vaginal infections and UTI, patient education Transvaginal ultrasound of cervical length is not supported for routine prenatal care: however, it recommended for high risk pregnancies: cervical length >30 mm has a height negative predictive value for delivery before 34 weeks (this measurement can be used to avoid unnecessary intervention)). Prevention

25. A 28 year old G5P3 is admitted to your office at 28 weeks’ gestation with regular painful uterine contractions every 3 minutes. Bimanual examination shows her cervix to be long and closed. Case Scenario

26. 1. Is this patient in preterm labor? It is not possible to make a diagnosis of preterm labor in this patient, because although she is experiencing regular uterine contractions her cervix is long and closed

27. 2.This patient had three prior spontaneous preterm deliveries at 28-31 weeks’ gestation and is very concerned that this pregnancy too will end prematurely. What tests are available to screen for preterm labor?

28. This woman is at high risk for preterm delivery. Screening tests currently available for the predection of preterm birth fall into three broad categories: 1)Risk factor scoring. 2)Assessment of cervical maturation. Transvaginal ultrasound is the “Gold standard”. The mean cervical length at 22-24 weeks’ gestation is 3.5 cm. a cervical length of <1.5cm at 22-24 weeks is predictive of delivery prior to 28 and 32 weeks in 60% and 90% of cases, respectively.

29. 3) Biochemical/endocrine markers. A number have been associated with preterm delivery, including activin, inhibin, follistatin, fibronectin, collagenase, progestrone, and estradiol-17Beta. To date only fetal fibronectin (fFN) is approved by the FDA in the US as a ascreening test for preterm birth. levels of fFN >50ng/ml in cervicovaginal secretions at 22-34 weeks are associated with premature birth, although the PPV of a positive fFN test at 22-24 weeks for spontaneos preterm birth prior to 28 weeks and 37 weeks is only 13% and 36%, respectively. The primary value of this test lies in its NPV:99.9% of patients with a negative fFN test will not deliver within 7 days and 98% will still be pregnant in 14 days.

30. 3.The patient continues to contract. A repeat cervical examination 4 hrs later shows her cervix to be 4 cm dilated and 90% effaced. You make a diagnosis of preterm labor and are considering initiating tocolytic therapy. Are there any contra indications to tocolysis?

31. In many instances, premature labor represents necessary escape of the fetus from a hostile intrauterine environment. As such, aggressive intervention to stop labor in such cases may be counter productive.

32. 4.Is antibiotic administration recommended? If so, what is the indication and for how long should treatment be continued? There are two reasons to administer antibiotics to women at imminent risk of preterm birth: 1)Antibiotics to prevent preterm birth. Broad spectrum antibiotic administration in the setting of PPROM<34 weeks’ gestation prolong latency, delay preterm birth, and improve short term perinatal outcome. 2)Chemoprophylaxis against GBS infection.

33. 5.You are considering starting a tocolytic agent. What is the goal of tocolysis? What tocolytic agents are available and which are most effective?

34. 6.Is there a place for progestrone to prevent birth? There is increasing evidence that progestrone supplementation from 16-20 weeks through 34-36 weeks may reduce the rate of pretem birth and improve short- term perinatal outcome.

35. Thank You for Listening…