preterm prediction and prevention--hernandez

7/30/2019 Preterm Prediction and Prevention--Hernandez

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Preterm Labor

Prediction, Prevention,and Management

Jennifer Hernandez, M.D.

Maternal-Fetal Medicine

Obstetrix Medical Group of Texas

Fort Worth, Texas


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Objectives

To review the background and epidemiology ofpreterm birth

To discuss risk factors and screening methods

available for predicting women at risk and toreview preventative options for those women atrisk

To review how to diagnose preterm labor andtreatment options available for those women

To discuss preterm labor in multi-fetal gestationsand how these differ from singleton pregnancies


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Overview


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Preterm Birth: Background

Preterm birth is defined as delivery prior to 37completed weeks gestation

Early preterm birth is defined as delivery priorto 34 weeks gestation

Late preterm birth is defined as deliverybetween 34 0/7- 36 6/7 weeks gestation

Preterm birth can be due to PTL (40-45%),PPROM (20-255%), or medically indicateddeliveries (30-35%)


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Preterm Birth: Epidemiology

The incidence ofpreterm birthincreased more than

20% from 1990 to2006

This was largely due

to a rise in multiplegestations andmedically indicatedlate preterm deliveries


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Preterm Birth: Epidemiology

Fortunately, the overall rate of preterm birth in theUnited States is decreasing, down to 11.7 percent in2011

This rate of preterm birth still remains higher thanother industrialized countries

The U.S. ranks 131st out 184 countries with reportedrates of preterm birth

Its not just a disparity between countries Vermont, New Hampshire, Oregon, and Maine all

have preterm birth rates < 9.6%

Louisiana, Mississippi, and Alabama all have rates

>14.6%


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Preterm Birth: Significance

Why does it matter?

Preterm birth is the leading cause of neonatal

morbidity and mortality Long-term sequelae include neurodevelopmental

deficits and increased risk of chronic disease inadulthood

Preterm birth costs the health care system$26 billion annually


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Preterm Birth: Significance

The risk of morbidityand mortalitydecrease as

gestational ageincreases, but therelationship is non-linear

The point with thelowest risk is between39 0/7 and 40 6/7weeks


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Prediction


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Preterm Birth: Risk Factors

Prior preterm birth The number one risk factor for preterm birth

The more preterm births, the stronger the risk of

recurrence:

One prior preterm birth: 14-22%

Two prior preterm births: 28-42%

More than 3 prior preterm births: 67% Most recurrent preterm births occur within 2

weeks of the gestational age of the prior pretermbirth


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Cervical and Uterine Factors

Short cervix There is an inverse relationship between cervical length by

ultrasound and gestational age at delivery More to come on this later.

Cervical surgery Ablative and excisional procedures for treatment of cervical

intraepithelial neoplasia have been associate with increasedrisk of preterm birth

Uterine malformations Congenital and acquired malformations are associated with

preterm birth


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Lifestyle factors

Smoking, Substance abuse

Body mass index

Physical activity, work, and stress

Demographic factors

Race

African Americans are at the highest risk for pretermbirth

Socioeconomic status

Educational status


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Infection Bacterial vaginosis and other vaginal infections

Asymptomatic bacteruria

Peridontal disease

Multiple gestation

Birth defects

Threatened abortion

Inter-pregnancy interval

Genetic factors


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Preterm Birth: Screening

Transvaginal cervicalultrasonography An increased risk of PTB as

cervical length shortens has

been observed in allpopulations

Cervical length below the10th percentile (25 mm) isconsistently associated with

an increased risk of PTB 90th percentile: 45 mm

50th percentile: 35 mm



2nd percentile: 15 mm


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Cervical length screening by history High risk population: Prior preterm birth < 34

weeks

Transvaginal ultrasound for cervical length every 2weeks from 16 to 24 weeks

Low risk population: No history of preterm birth One time transabdominal screening at anatomy

ultrasound (usually ~18 weeks) with transvaginalultrasound only if first measurement concerning


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Fetal Fibronectin

A basement membrane protein produced by the fetalmembranes

Thought to act as an adhesion molecule that binds theplacenta and membranes to the uterine decidua

Rarely found in the vagina after 20 weeks gestation in anormal pregnancy

When found in the vagina after 20 weeks, it has been

associated with an increased risk of spontaneous PTB

Low sensitivity, high specificity

ACOG no longer recommends its use as a screening tool


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Home uterine activity monitoring

Not recommended

Bacterial vaginosis screening

Not recommended


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Prevention


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Preterm Birth: Prevention

History

17-hydroxyprogesterone caproate injections

Any woman with a singleton gestation and prior

spontaneous preterm delivery should receive weeklyprogesterone injections from 16 to 36 weeks

Use of progesterone in these high risk patients hasbeen shown to significantly reduce the risk of recurrent

preterm birth This is thought to reduce inflammation, maintain

cervical integrity, and antagonize oxytocin


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Preterm Birth: Prevention

Cervical length

High risk patients

Cerclage

If cervical length < 25 mm prior to 24 weeks Associated with a 30% reduction in preterm birth along with

decreased perinatal morbidity and mortality

Low risk patients

Vaginal progesterone If cervical length is < 20 mm prior to 24 weeks

Associated with ~ 45% reduction in preterm birth

Cerclage Has not been shown to significantly reduce preterm birth

rate, even at cervical lengths < 15 mm


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Management


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Preterm Birth: Symptoms

Cramping

Contractions

Low back pain Lower abdominal pressure

Vaginal discharge


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Preterm Birth: Diagnosis

Its not preterm labor without cervical change

Contractions alone without cervical changecarry a 40-70% false-positive rate

Fetal fibronectin

The value is in its negative predictive value

>99% for delivery within 14 days

Positive predictive value Only 13-33% (!) for delivery in 7-10 days


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Preterm Birth: Intervention

Tocolytics The goal of tocolysis is for short-term prolongation of

pregnancy to allow administration of antenatal

steroids a well as maternal transport if needed No evidence exists that tocolytic therapy has any

direct favorable effect on neonatal outcomes

Long-term use of any of these agents carries a high

risk for side effects both maternal and fetal A few examples: Magnesium sulfate, Calcium channel

blockers (Nifedipine), NSAIDs (Indomethacin), Beta-adrenergic receptor antagonists (Terbutaline)


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Antenatal corticosteroids This is the single most beneficial intervention for

improved neonatal outcomes in patients who deliver

preterm Neonates whose mothers receive steroids have

significantly lower severity and frequency ofrespiratory distress syndrome, intracranialhemorrhage, necrotizing enterocolitis, and death(compared to those who do not receive steroids)

Betamethasone and Dexamethasone are the mostwidely studied corticosteroids and are equivalent inefficacy


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Antenatal corticosteroids A single course of steroids is recommended for any

woman at risk for preterm delivery between 24 and 34

weeks A single rescue course at least 2 weeks after the first

course has additional neonatal benefit

However, regularly scheduled repeat courses are not

recommended


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Antibiotics

It has been theorized that infection orinflammation are associated with contractions

However, it has never been shown that antibiotictreatment in women with preterm labor and intactmembranes have any benefit in prolonging thepregnancy

This is different than the important antibioticprophylaxis for GBS prophylaxis and in the settingof rupture of membranes


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Neuroprotection

Pre-delivery administration of magnesium sulfatereduces the occurrence of cerebral palsy

Magnesium sulfate should be given with the intentfor neuroprotection when birth is anticipated priorto 32 weeks

Same protocol essentially as magnesium fortocolysis and preeclampsia seizure prophylaxis


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Multiples


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Preterm Birth: Multiples

In 2006, 60% of twins and 93% of triplets wereborn preterm

Unfortunately, many of the strategies listed

previously are ineffective or actually detrimentalin a multi-fetal pregnancy

Progesterone treatment does not reduce theincidence of preterm birth

Cerclage may actually increase the risk of pretermbirth not recommended

Tocolytics carry a much higher risk of side effects inthis population


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Preterm Birth: Multiples

There is not even adequate data todemonstrate benefit from the use of antenatalsteroids in multiple gestations

However, because of the clear benefitattributable to corticosteroids in singletongestations, steroids are readily utilized in

multiple gestations The same concept applies to magnesium

sulfate for neuroprotection


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Conclusions


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Preterm Birth: Conclusions

Preterm birth remains a commoncomplication for many women in the UnitedStates

It carries a huge financial burden for familiesaffected as well as the health care system asa whole

There are multiple risk factors for pretermbirth, but a prior history of this event is thestrongest predictor of recurrence


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There are few reliable methods of predictionavailable maternal history and cervicallength

There are even fewer reliable methods ofprevention once an increased risk of pretermdelivery is identified progesterone and

cerclage Preterm labor can be elusive at times


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Once preterm labor is diagnosed, severaltreatments are available to reduce theneonatal morbidity and mortality if preterm

birth occurs antenatal steroids andmagnesium sulfate

Multifetal gestations have a very high risk of

preterm birth, but unfortunately, effectiveprevention and management options arelimited in this setting


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Questions?


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Thank you!


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References

Prediction and prevention of preterm birth. ACOG Practice Bulletin Number 130, October2012.

Cunningham FG, Leveno KJ, Bloom SL, et al. Williams Obstetrics. 23rd edition. McGrawHill. 2010.

Goldenberg RL, Mercer BM, Meis PJ., et al. The preterm prevention study: fetal fibronectintesting and spontaneous preterm birth. Obstet Gynecol. 1996;87:643-48.

Goldenberg RL, Iams JD, Das A., et al. The preterm prevention study: sequential cervical

length and fetal fibronectin testing for the prediction of spontaneous preterm birth. Am JObstet Gynecol 2000;182:636-43. Iams JD, Geldenberg RL, Meis PJ, et al. The length of the cervix and the risk of

spontaneous premature delivery. NEJM 1996;334:567-72. Lockwood CJ, Senyei AE, Dische MR, et al. Fetal fibronectin in cervical and vaginal

secretions as a predictor of preterm delivery. NEJM 1991;325:669-74. To MS, Alfirevic Z, Heath VC, et al. Cervical cerclage for prevention of preterm delivery in

women with short cervix: a randomised controlled trial. Lancet 2004;363:1849-53.

Goya M, Pratcorona L, Merced c, et al. Cervical pessary in pregnant women with a shortcervix (PECEP): an open label randomised controlled trial. Lancet 2012;379:1800-6.

Rouse DJ, Caritis SN, Peaceman aM, et al. A trial of 17 alpha-hydroxyprogesteronecaproate to prevent prematurity in twins. NEJM 2007:357:454-61.

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