PRETERM LABOR

Melissa Tebrock MD

MAJ, MC, USA

Dewitt Army Community Hospital

9 June 2005

Disponible en:http://www.usuhs.mil/fap/capcon/256,1,PRETERM LABOR

Preterm Labor

• Definition

• Incidence

• Etiology

• Prevention/Surveillance

• Diagnosis

• Management

Preterm Labor (PTL)

ACOG defines Preterm Labor as regular contractions with cervical change before 37

weeks’ gestation

PTL: Incidence

• 10-12% of all pregnancies

• Related to 80% of perinatal mortality

• Single greatest cause perinatal morbidity and mortality in western countries

• Most common cause of hospitalization during pregnancy

Preterm Delivery (PTD)

• Despite medical advances, PTL and preterm births rates not improving

• Medical advances = greater # complicated pregnancies and successful PTD

• Rate of U.S. preterm birth increasing • 1995: 25th in world infant mortality• Huge health care costs • Continued ethical concerns

PTL Outcomes

• Developmental delay

• Cerebral Palsy & neurological deficits

• Poor school grades

• Chronic pulmonary issues

• vision//hearing impairment

• Family, school, economic burden

PTL: Risk Factors

• Maternal Factors:– Age (<18 and >40)

– Race (nonwhite)

– Poverty

– Smoking

– Drugs/EtOH

– Prior preterm birth

• Maternal Factors:– Prior 2nd trimester loss

or bleeding

– Psychological stress

– Poor nutrition

– Low prepregnancy weight and gain

PTL: Risk Factors:

• Uterine:• Anatomic anomaly:

-fibroids, placenta previa

• Increased volume:-multiple gestation, polyhydramnois

• Trauma/abruption• Cervical incompetence/short cervix• Oligohydramnios

PTL and Infection

• History of previous genital infection

• Current genital infection

• Current systemic infection, i.e. pneumonia, periodontal disease, appendicitis

PTL: Genital Infections

• Often subclinical• Correlate more w/ PTL/PTB < 31 wks• Anaerobes and genital mycoplasmas• Ascend vagina, cervix, triggers leukocyte

recruitment, cytokine production, enzymes which weaken protective cervical mucous, cause PTL & preterm premature rupture of membranes

PTL: Genital Infections

• Chorioamnionitis• Chlamydia & gonorrhea: irritate cervix• Group B Streptococcus: amniotic irritation• Asymptomatic bacturia, UTI, Pyelonephritis• +/- Trichomonas, Candida, Ureaplasma

urealyticum, Mycoplasma hominis

PTL and Bacterial Vaginosis

• Known association between PTL and BV• Found in 10-25% pregnant women, <3%

will have issues• 50% asymptomatic• Treatment of BV in high risk women

shown to PPROM, not necessarily PTL• Trials for screening and treatment have

varying results

Etiology PTL

Often multifactorial

Often idiopathic

No risk factors in 50% of preterm births

Preterm Premature Rupture of Membranes (PPROM)

• PPROM: rupture membranes prior to 37 weeks and at least 1 hour before onset labor

• Ave 8% all pregnancies

• 20-40% before 37 weeks

• Same Risk Factors as PTL– Infection often the culprit

PTL: Prevention and Early Detection

Education Programs: no evidence of efficacy in low risk pregnancy

Intensive education in high-risk groups has not decreased PTD rates in US

Effective in Europe

Home Uterine Activity Monitoring (HUAM)

• Theory: patients may not recognize early uterine activity associated with PTD

• HUAM studied as method to predict preterm labor in high risk women

• Tocodynamometer readings, daily phone calls from RN/provider

• Mixed study results, insufficient data and cost have limited applicability

Risk Scoring Systems

Multiple scoring systems devised

No one better than another

Unsuccessful in predicting PTL

May have role in predicting PTD

Transvaginal Cervical Ultrasonography

• Provides reliable length, dilation, effacement– More accurate than digital exam– Risk PTD w/ cervix length

• PPV 43%, NPV 89% if > 2.5 cm for PTD, accepted safe length is 3 cm

• Not currently recommended for routine screening• Use in high risk/symptomatic patients• Cervical funneling also useful predictor for

PTL/PTD- more study needed

Biochemical Markers

• Multiple markers for PTL found:– Fetal fibronectin– Salivary Estriol– IL-6– Estradiol-17B– Progesterone

• Not currently recommended as routine screening tools

Fetal Fibronectin (FFN)

• Present throughout body, in blood• Is a glue like substance that helps maintain

placental attachment to the decidua • Not detectable in vaginal secretions after 20

weeks to term• If present after 20 weeks in cervical/vaginal

fluids= disruption maternal-fetal boundaries• Negative if < 50g/ml

Fetal Fibronectin

• High specificity: after a negative test, 124 of 125 women will not deliver in next 14 days

• Positive result: 1 in 6 women will deliver in next 14 days (does not=delivery)

• May aid in early discharge vs. increased vigilance

• FDA approved

Progesterone and PTL Prevention

• Inhibits oxytocin effect of prostaglandin F2a and stimulation of alpha adrenergics, acting as a tocolytic

• No known teratogenic effects

• May cause pain, swelling, bruising from injection, but no known maternal/fetal metabolic or hemodynamic effects

Progesterone and PTL Prevention

• Multiple studies show weekly IM injection of 250-1000 mg alpha-hydroxyprogesterone caproate from 16-37 weeks in women at risk for PTL reduced PTD rates, w/ NNT range 2.4-7

• ? Reduced NEC, IVH, perinatal morbidity• Other studies did not demonstrate benefit• NOT FDA approved & not ACOG recommended

Asymptomatic Infection Screening and Antibiotic

Prophylaxis• Some evidence to screen for asymptomatic

bacturia, though not currently recommended• No recommendation to screen for BV

routinely• Screen, treat based on risk, symptoms,

personal comfort level• Prophylaxis in asymptomatic women not

recommended

PTL/PPROM Evaluation

• History:– Ask about Risk Factors– Dating (preterm)– Onset symptoms (back pain, pressure, cramps,

contractions, fluid leak, bleeding)– Other medical history

PTL/PROM Exam

• Maternal vitals: temp, BP, P, RR

• Maternal quick physical

• Fetal heart rate (FHR) pattern

• Contraction pattern

• Fetal size, presentation

• DO NOT DO DIGITAL EXAM IF ROM SUSPECTED OR WILL DO FFN TEST!

PTL/PPROM Exam

• Sterile Speculum Exam:– Look for pooling, trailing membranes– Nitrazine, ferning

• Cervix visualization

• FFN if available

• Wet prep, cultures (GBS, GC, Chl)

PTL/PPROM studies

• Ultrasound:– cervix length, AFI, gestational age

• CBC, UA: r/o infection

• Preeclampsia labs as needed

• Amniocentesis for lung maturity as needed

PTL

• 4 contractions in 20 minutes or• 8 contractions in 60 minutes with

• PROM

• Progressive cervical change

• Effacement greater than 80%

• Cervical dilation greater than 1 cm

• Dilation >3cm, positive FFN concerning regardless of presence of contractions

Initial Thoughts

• Hydration, bed rest, pelvic rest– No evidence this is beneficial

• Consider early transfer– Is delivery imminent?– Condition mother and fetus– Capabilities your/transfer center

Medical Management of Preterm Labor

• Steroids

• Tocolysis

• Antibiotics

PTL: Steroids

• Reduces RDS, IVH, NEC, infant mortality

• Only treatment shown to improve fetal survival in PTL

• Criteria:– Delivery likely within 7 days– fetus 24-34 weeks – Able to delay delivery 24-48 hrs

PTL: Steroids

• Use between 32-34 weeks arguable- may no benefit RDS but may benefit IVH up to 34 weeks

• Regimens:-Betamethasone 12 mg IM, 2 doses, q 24 hr -Dexamethasone 6 mg IM, 4 doses, q 12 hr

PTL: Steroids

• Maternal Adverse Effects– Short term: glucose control, pulmonary edema,

infection– Long term: no adverse effects

• Fetal Adverse Effects– No long term effects of single course– Multiple course associated w/ infection,

abnormal development

Tocolysis

Only evidence showing acute tocolysis is beneficial for short term PTL management, and not for PTD

No evidence that maintenance tocolysis is beneficial fro PTL or PTD at this time in large studies

PTL: Tocolysis

• Goal: prolong pregnancy 2-7 days for steroid efficacy and transfer to higher level of care,

• Goal: reduce contractions (< 6/hr) and stop cervical change

Tocolysis

• Criteria:-Assure maternal/fetal well being first– no contraindication to rx– no contraindication to prolonging pregnancy– Diagnosis clear– Cervix <4cm– 24-34 weeks

Tocolysis

• General Contraindications– Acute fetal distress– Chorioamnionitis– Severe preeclampsia/eclampsia– Fetal demise– Fetal maturity– Maternal hemodynamic instability

Tocolytic Agents

• Beta-mimetics– Ritodrine, terbutaline

• Magnesium Sulfate

• Indocin

• Nifedipine (CCBs)

Beta-mimetics

• Function:– Stimulate beta2 receptors in uterus and lung, decrease

contractility– Cross react with beta2 in heart

• Efficacy: shown to prolong labor 24-48 hours to allow transfer and steroid benefits

• Ritodrine (FDA approved) and Terbutaline• Neither beneficial to neonatal mortality, but

studies done prior to steroid use

Beta-mimetics

Terbutaline– IV and multiple SC dosing effective in temporarily

stopping contractions– SC 0.25 mg q 1-4 hours– IV 0.01 mg/min, 0.005 mg/min to maximum of 0.025

mg/min– Oral dose not effective in PTL (ok for PTCx)

Ritodrine: iv only, 0.1 mg/min, increase by 0.05 mg/min q 30 minutes, titrate down & stop 12 hours after contractions stopped (max 0.35 mg/min)

Maternal Side Effects: Beta-mimetics

• Tremor, nervousness, HA, N/V, anxiety, SOB, palpitations, chest pain

• Hyperglycemia, electrolyte abnormalities

• Fluid retention, hyperkinesias

• Hypotension, pulmonary edema, arrhythmias, MI, tachyphylaxis

Fetal Side Effects of Beta-mimetics

• Tachyarrhythmia, heart failure, MI, hypotension

• Hyper/hypoglycemia, hyperbilirubinemia

• Death

Contraindications: Beta-mimetics

• Absolute:

• Maternal cardiac disease, eclampsia, severe pre-eclampsia, hemorrhage, uncontrolled hyperthyroid, diabetes

• Relative:

• Diabetes, hypertension, migraines, sepsis

Magnesium Sulfate

• Widespread use• No clear evidence showing efficacy in

delaying/preventing PTD• Controversy: ?may increase infant mortality, but

studies show less gross motor dysfunction in infants

• ? Works by calcium antagonist activity• Load 4-6 gm IV, then 1-4 gm/hour, no wean• Oral dose not effective

Magnesium Sulfate

• Side effects:– N/V, HA, warmth, sweating, flushing, hypocalcemia,

tetany, muscular paralysis, hypotension, palpitations, pulmonary edema, respiratory arrest (toxic levels), cardiac arrest (rare)

– Pulmonary edema worse when used with terbutaline

• Crosses placenta, no adverse fetal effects (may have less reactivity)

Magnesium Sulfate

• Contraindications:– Myasthenia Gravis, renal failure, hypocalcemia

• Exam:– Fluid I/O, UOP, VS, mental status hourly– Pulm exam– Reflexes (loss when level >8)– Therapeutic level: 5.5-7.5 mg/dl, toxic >15– Antidote: calcium gluconate

Indocin

• Inhibits prostaglandins/cytokines that trigger labor• Well studied, use limited by side effects• Can inhibit PTL for 48 hrs in <37 weeks• Use in cases w/ good dating, <32 weeks • Dosing:

– 100mg rectal dose, repeat x1 in 1-2 hours if contractions persist

– 25-50 mg orally q4-6 hours <48 hours for cessation of contractions

Indocin

• Well tolerated by mom, causing usual NSAID side effects

• Does not decrease neonatal mortality, may increase IVH, jaundice, NEC risk after 32 weeks

• Can cause PPH, constrict fetal ductus arteriosis, oligohydramnios

Nifedipine

• Inhibit contraction of smooth muscle

• Very efficacious

• Nifedipine most widely studied CCB

• Some studies show as efficacious or better than beta-mimetics with less side effects

• Gaining popularity as tocolytics of choice

Nifedipine

• Fetal effects:– No adverse fetal effects– No increase congenital anomalies

• Maternal effects:– Flushing dizziness, nausea, hypotension– Contraindicated if hypotensive, cardiac disease

or hemorrhage

Nifedipine

• Dosing:– 30 mg oral dose load– 10-20 mg po q 4-6 hours

Antibiotics

• If have specific infection, treat• If known GBS+, treat (no benefit PTL, but

decrease transmission to infant)• Empiric antibiotics in PTL w/ intact membranes:

– Conflicting results: no short/long term benefits, delay of PTD

• Ampicillin 2 gms iv q 6 hours (macrolides also effective) often used if unclear GBS/possible infection

• USE IN PPROM- beneficial

PROM/PPROM

If >36 weeks, manage as PROM

If <32 weeks, manage as PPROM

If 32/36 weeks, weight amniocentesis, weight, options

PPROM Management

• Delivery likely within 12-24 hours– Tertiary care center w/ NICU– Tocolysis, steroids– Antibiotics for GBS– Avoid digital exams

• Expectant management in delivery not imminent

Delivery of Premature Infant

• Anticipate malpresentation

• Limit narcotics

• Delivery <10 cm dilation

• NICU team

ACOG Recommendations for PTL Management (5/03):

No clear first-line tocolytic drugs for PTL Circumstances dictate treatment

Antibiotics do not appear to prolong gestation and should be reserved for GBS prophylaxis in imminent delivery

Neither maintenance tocolysis or repeated acute tocolysis improve perinatal outcome

ACOG Recommendations for PTL Management (5/03):

Tocolytic drugs may prolong pregnancy for 2-7 days, allowing for steroids administration to improve fetal lung maturity and maternal transport

Bed Rest, hydration and pelvic rest do not appear to improve PTD rates and should not be routinely recommended

References

1. Williams Obstetrics, 21st Edition, McGraw-Hill, pp. 689-728.2. Advanced Life Support in Obstetrics provider course syllabus, Chapter D, Preterm labor and

premature rupture of membranes. 4th ed. Leawood, Kan.: American Academy of Family Physicians, 2000.

3. American College of Obstetricians and Gynecologists. Assessment of risk factors for preterm birth. Practice Bulletin no.31. Washington D.C.: ACOG, 2001.

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References

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13. Sanchez-Ramos L, Huddleston JF. The therapeutic value of maintenance tocolysis: an overview of the evidence. Clinics in Perinatology Dec 2003; 30(4): 841-54.

14. Peaceman AM, Andrews WW, Thorp JM, Cliver SP, Lukes A, Iams JD, Coultrip L, Eriksen N, Holbrook RH, Elliott J, Ingardia C, Pietrantoni M. Fetal Fibronectin as a predictor of preterm birth in patients with symptoms: a multicenter trial. American Journal of Obstetrics and Gynecology Jul 1997; 177(1): 13-8.

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