1. Preventing Preterm Birth Kerri Thompson Advisor: Dr. Eric Reynolds

2. Background Preterm birth= infants delivered after 20wks and before 37wks gestation The incidence of preterm birth has increased; 12% of births in the U.S. Account for the vast majority of perinatal mortality (around 80%) and about 50% of the long-term neurologic disability Not well understood

3. Preterm Labor Complex process- possible relationship between infection and inflammation with PTL Braxton-Hicks contractions spontaneously resolve Diagnosis is difficult but must be made in time it administer therapy Consider contraindications to stopping PTL

4. Risk Factors Previous preterm birth Women pregnant with twins, etc. Uterine or cervical abnormalities i.e. incompetent cervix Premature membrane rupture Short time between pregnancies Diabetes, HTN Younger/older women African-American women have a 2-fold increase in PTB BMI<20 or obesity Infection Smoking, drinking, drugs Stess, working long hrs Late/no prenatal care 2 nd trimester bleeding

5. Important info for PAs Screen women for risk factors and enroll in PTL education programs by 18wks gestation if they are at risk Seek immediate medical care if they experience signs of PTL Basic signs are contractions every 10 minutes or more often, change in vaginal discharge like bleeding, pelvic pressure, low dull backache, cramping as with a period, or abdominal cramps with or without diarrhea

6. Prevention Goals The goal of tocolytic therapy is to delay labor so the fetus can mature safely by delaying birth long enough to administer corticosteroids or to hopefully reach term Steroids speed up the lung maturation to enable the infant to breathe better after birth Allow time to treat maternal infection or transfer to a tertiary care facility better equipped for PTB Poor understanding of mechanisms involving tocolytics, PTL, inadequate research

7. Treatment Options Bedrest- fairly inexpensive, typically safe, easily available, may offer some benefit Lateral recumbent position relieves pressure of the uterus on the maternal great vessels, augmenting uterine blood flow, enhancing right atrial return, and maternal cardiac output Assoc. maximal oxygenation and nutrient availability may decrease prostaglandin production (thought to be 1° triggers of PTL) Worry about clots, anxious/depressed feelings, not proven efficacy

8. Cervical Cerclage Can be used to prevent PTD in structural cervical defects such as a weak cervix or a short cervical length on transvaginal ultrasonography surgical procedure closing the bottom half of the endocervical canal with a stitch until the 37-38 week of pregnancy Mixed results, may only be an appropriate choice for true cervical incompetence Potential risks- premature contractions, membrane rupture, cervical infection, cervical laceration if not removed before delivery, and cervical dystocia (unable to dilate normally)

9. Antibiotic Treatment Infection is a strong risk factor for PTL Should be started as early as possible because once the inflammatory process has begun, stopping labor may be quite difficult or possibly inappropriate In PPROM, may significantly reduce the risk for chorioamnionitis, delay delivery 48hrs to 7days, and reduce neonatal mortality Data has been conflicting

10. Progesterone Necessary part of a normal pregnancy 17α-hydroxyprogesterone was shown to decrease the incidence of PTB and the # of infants weighing less than 2500g at birth Rates of PTD at <37, <35, and <32 wks gestation were reduced, but ineffective in preventing PTB of twins in another study Lower rates of necrotizing enterocolitis, need for supplemental oxygen, and intraventricular hemorrhage and no teratogenic/fetotoxic effects ACOG recommends the use of progesterone supplementation should be restricted to women with a documented history of prior spontaneous PTD Promising but limited information on benefit or harm

11. Magnesium Sulfate First-line tocolytic is due to its familiarity, ease of use, and almost absence of serious maternal AEs minor side effects- feeling hot/flushed, n/v, blurred/double vision, or lethargic Lethargy, hypotonicity, and low Apgar scores are the primary side effects in neonates Stops 96% of PTL without cervical changes and 75-85% with cervical changes A meta-analysis showed no substantial effect on the proportion of women delivering within 48hrs

12. β-sympathomimetic Terbutaline is β2-receptor specific which is the receptor causing uterine relaxation and has replaced ritodrine If contractions continue after 2 treatments, most clinicians switch to Mag. Sulfate SEs- flushing, tachycardia, palpitations, hypotension, cardiac arrhythmias, chest pain, EKG changes, and myocardial ischemia with the most common serious AE being pulmonary edema β-agonists are better in prolonging pregnancy 3- 7 days and increasing birth weight, but have not shown a significant reduction in perinatal M & M

13. Calcium Channel Blockers Initial choice in Europe, but remain 2nd line treatment in the U.S. Appeal- effectiveness, ease of oral administration, rapid onset of action, tolerable SE, & lack of known neonatal AE Reduced # of women giving birth within 7 days of treatment and before 34wks of gestation, assoc. with a reduction in neonatal RDS, necrotizing enterocolitis, intraventricular hemorrhage, and neonatal jaundice SE- dizziness, lightheadedness, HA, flushing, nausea, and transient hypotension MgSO4 and Nifedipine should not be used together

14. Antiprostaglandin synthetase inhibitors Prostaglandins are key components in the labor process Indomethacin- nonspecific COX-1 & 2 inhibitor Reduces the # of deliveries within 48hrs & before 37wks, but due to concern over the SEs, it is typically used only when other therapies fail Fetus should be monitored for signs of ductal constriction or oligohydramnios and could mask chorioamnionitis and may independently increase the rate of NE and grade III to IV intraventricular hemorrhage Compared with β-mimetics, MGSO4, and atosiban… indomethacin proved superior in tocolytic efficacy without an increase in neonatal or maternal morbidity

15. Oxytocin receptor blocker Oxytocin is believed to play a role in human labor, but extent is controversial Atosiban has been shown to have the same efficacy as other tocolytics but with fewer SE and has been successful as a maintenance therapy SE- n/v, headaches, and chest pain, no known AE in the infant Not enough data is available yet for atosiban to be widely accepted

16. Comparison Pregnancy was prolonged more than 48 hours significantly more frequently in patients receiving nifedipine when compared to β-agonists When compared to magnesium sulfate, there was no difference in efficacy, but nifedipine was better tolerated When indirectly compared with atosiban, nifedipine is more effective and is assoc. with a significant reduction in RDS, but when directly compared the efficacy was the same, but the AE of nifedipine were significantly more

17. Conclusion Until the controversy with indomethacin use is resolved and atosiban is better researched, nifedipine, a calcium channel blocker, appears to be the preferred tocolytic due to its efficacy and tolerability