Preventing Preterm BirthPreventing Preterm Birth

Kerri ThompsonKerri Thompson

Advisor: Dr. Eric ReynoldsAdvisor: Dr. Eric Reynolds

BackgroundBackground

Preterm birth= infants delivered after Preterm birth= infants delivered after 20wks and before 37wks gestation20wks and before 37wks gestation

The incidence of preterm birth has The incidence of preterm birth has increased; 12% of births in the U.S.increased; 12% of births in the U.S.

Account for the vast majority of perinatal Account for the vast majority of perinatal mortality (around 80%) and about 50% of mortality (around 80%) and about 50% of the long-term neurologic disabilitythe long-term neurologic disability

Not well understood Not well understood

Preterm LaborPreterm Labor

Complex process- possible relationship Complex process- possible relationship between infection and inflammation with between infection and inflammation with PTLPTL

Braxton-Hicks contractions spontaneously Braxton-Hicks contractions spontaneously resolveresolve

Diagnosis is difficult but must be made in Diagnosis is difficult but must be made in time it administer therapytime it administer therapy

Consider contraindications to stopping PTLConsider contraindications to stopping PTL

Risk FactorsRisk Factors

Previous preterm birth Previous preterm birth

Women pregnant with Women pregnant with twins, etc.twins, etc.

Uterine or cervical Uterine or cervical abnormalities i.e. abnormalities i.e. incompetent cervix incompetent cervix

Premature membrane Premature membrane rupture rupture

Short time between Short time between pregnancies pregnancies

Diabetes, HTNDiabetes, HTN

Younger/older women Younger/older women

African-American women African-American women have a 2-fold increase in have a 2-fold increase in PTBPTB

BMI<20 or obesityBMI<20 or obesity

Infection Infection

Smoking, drinking, drugsSmoking, drinking, drugs

Stess, working long hrsStess, working long hrs

Late/no prenatal careLate/no prenatal care

22ndnd trimester bleeding trimester bleeding

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

Prevention GoalsPrevention Goals

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

Treatment OptionsTreatment OptionsBedrestBedrest- fairly inexpensive, typically safe, easily - fairly inexpensive, typically safe, easily available, may offer some benefitavailable, may offer some benefit

Lateral recumbent position relieves pressure of Lateral recumbent position relieves pressure of the uterus on the maternal great vessels, the uterus on the maternal great vessels, augmenting uterine blood flow, enhancing right augmenting uterine blood flow, enhancing right atrial return, and maternal cardiac output atrial return, and maternal cardiac output

Assoc. maximal oxygenation and nutrient Assoc. maximal oxygenation and nutrient availability may decrease prostaglandin availability may decrease prostaglandin production (thought to be 1production (thought to be 1° triggers of PTL° triggers of PTL))

Worry about clots, anxious/depressed feelings, Worry about clots, anxious/depressed feelings, not proven efficacynot proven efficacy

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

Antibiotic TreatmentAntibiotic Treatment

Infection is a strong risk factor for PTLInfection is a strong risk factor for PTL

Should be started as early as possible because Should be started as early as possible because once the inflammatory process has begun, once the inflammatory process has begun, stopping labor may be quite difficult or possibly stopping labor may be quite difficult or possibly inappropriate inappropriate

In PPROM, may significantly reduce the risk for In PPROM, may significantly reduce the risk for chorioamnionitis, delay delivery 48hrs to 7days, chorioamnionitis, delay delivery 48hrs to 7days, and reduce neonatal mortality and reduce neonatal mortality

Data has been conflictingData has been conflicting

ProgesteroneProgesteroneNecessary part of a normal pregnancyNecessary part of a normal pregnancy17α-hydroxyprogesterone was shown to decrease the 17α-hydroxyprogesterone was shown to decrease the incidence of PTB and the # of infants weighing less than incidence of PTB and the # of infants weighing less than 2500g at birth2500g at birthRates of PTD at <37, <35, and <32 wks gestation were Rates of PTD at <37, <35, and <32 wks gestation were reduced, but ineffective in preventing PTB of twins in reduced, but ineffective in preventing PTB of twins in another studyanother studyLower rates of necrotizing enterocolitis, need for Lower rates of necrotizing enterocolitis, need for supplemental oxygen, and intraventricular hemorrhage supplemental oxygen, and intraventricular hemorrhage and no teratogenic/fetotoxic effects and no teratogenic/fetotoxic effects ACOG recommends the use of progesterone ACOG recommends the use of progesterone supplementation should be restricted to women with a supplementation should be restricted to women with a documented history of prior spontaneous PTD documented history of prior spontaneous PTD Promising but limited information on benefit or harmPromising but limited information on benefit or harm

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

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

Calcium Channel Blockers Calcium Channel Blockers Initial choice in Europe, but remain 2nd line Initial choice in Europe, but remain 2nd line treatment in the U.S.treatment in the U.S.Appeal- effectiveness, ease of oral administration, Appeal- effectiveness, ease of oral administration, rapid onset of action, tolerable SE, & lack of known rapid onset of action, tolerable SE, & lack of known neonatal AE neonatal AE Reduced # of women giving birth within 7 days of Reduced # of women giving birth within 7 days of treatment and before 34wks of gestation, assoc. treatment and before 34wks of gestation, assoc. with a reduction in neonatal RDS, necrotizing with a reduction in neonatal RDS, necrotizing enterocolitis, intraventricular hemorrhage, and enterocolitis, intraventricular hemorrhage, and neonatal jaundice neonatal jaundice SE- dizziness, lightheadedness, HA, flushing, SE- dizziness, lightheadedness, HA, flushing, nausea, and transient hypotension nausea, and transient hypotension MgSO4 and Nifedipine should not be used togetherMgSO4 and Nifedipine should not be used together

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

Oxytocin receptor blocker Oxytocin receptor blocker

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

ComparisonComparison

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

ConclusionConclusion

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