Preterm Labor and Delivery

UNC School of MedicineObstetrics and Gynecology Clerkship

Case Based Seminar Series

Objectives for Preterm Labor

Identify the risk factors and causes for preterm labor

Describe the signs and symptoms of preterm labor

Describe the initial management of preterm labor

List indications and contraindications of medications used in preterm labor

Identify the adverse outcomes associated with preterm birth

Counsel the patient regarding risk reduction for preterm birth

“Regular” uterine contractions With

Cervical “change” or > 2 cm dilation or > 80% effacement

Definition: Preterm Labor

Preterm birth: < 37completed weeks Very Preterm birth: < 32 weeks Extremely Preterm birth: < 28 weeks

Preterm Delivery

12.5% USA (2004) 2% < 32 weeks Fetal growth

Small for gestational age < 10th % for GA

Birthweight: Low BWT < 2500 grams Very low BWT < 1500 grams Extremely low BWT < 1000 grams

Incidence

13% Rise in PTB since 1992 Multiple gestation (20% increase)

50 % twins, 90% triplets born preterm

Changes in Obstetric management Ultrasound, induction

Sociodemographic factors AMA!

No improvement with physician interventions!

Incidence

Neonatal deaths

Percentage of neonatal deaths

Disorders related to prematurity and low birth weight 4,318 23.0

Congenital malformations, chromosomal abnormalities 4,144 22.1

Maternal complications 1,394 7.4

Placenta, cord, and membrane complications 1,049 5.6

Respiratory distress 929 4.9

Bacterial sepsis 737 3.9

Intrauterine hypoxia and birth asphyxia 589 3.1

Neonatal hemorrhage 563 3.0

Atelectasis 483 2.6

Necrotizing enterocolitis 313 1.7

Neonatal deaths: death within 28 days of birth .Data adapted from: the Centers for Disease Control and Prevention, 2000.

Leading Causes of Neonatal Death (USA)

Infant mortality Over 50% of infant deaths occur among the 1.5% infants

< 1500 grams 70 % of infant deaths occur among the 7.7% of infants

< 2500 grams Morbidity

60%: 26 weeks 30%: 30 weeks

Significance

Infant Mortality

Infant Morbidity

Infant Morbidity

Non-modifiablePrior preterm birth

African-American race

Age <18 or >40 years

Poor nutrition/low pre-pregnancy weight

Low socioeconomic status

Cervical injury or anomaly

Uterine anomaly or fibroid

Premature cervical dilatation (>2 cm)or effacement (>80 percent)

Over distended uterus (multiple pregnancy, polyhydramnios)

? Vaginal bleeding

? Excessive uterine activity

Modifiable Cigarette smoking

Substance abuse

Absent prenatal care

Short interpregnancy intervals

Anemia

Bacteriuria/urinary tract infection

Genital infection

? Strenuous work

? High personal stress

Risk Factors for Preterm Birth

Stress Single women Low socioeconomic status Anxiety Depression Life events (divorce, separation, death) Abdominal surgery during pregnancyOccupational fatigue Upright posture Use of industrial machines Physical exertion Mental or environmental stressExcessive or impaired uterine distention Multiple gestation Polyhydramnios Uterine anomaly or fibroids Diethystilbesterol

Cervical factors History of second trimester abortion History of cervical surgery Premature cervical dilatation or

effacementInfection Sexually transmitted infections Pyelonephritis Systemic infection Bacteriuria Periodontal diseasePlacental pathology Placenta previa Abruption Vaginal bleeding

Risk Factors for Preterm Birth

Miscellaneous Previous preterm delivery Substance abuse Smoking Maternal age (<18 or >40) African-American race Poor nutrition and low body mass index Inadequate prenatal care Anemia (hemoglobin <10 g/dL) Excessive uterine contractility Low level of educational achievement Genotype

Fetal factors Congenital anomaly Growth restriction

Risk Factors for Preterm Birth

Prior preterm birth: Increases risk in subsequent pregnancy Risk increases with

more prior preterm births earlier GA of prior preterm birth (s)

Risk Factors for Preterm Birth

Prior PTD @ (23-27 wks) 27% Prior PPROM 13.5%

Prediction/Recurrence

First Birth Second Birth Subsequent Preterm Birth (%)

Not Preterm 4.4

Preterm 17.2

Not Preterm Not Preterm 2.6

Preterm Not Preterm 5.7

Not Preterm Preterm 11.1

Preterm Preterm 28.4

Prediction/Recurrence

80% of Preterm births are spontaneous 50% Preterm labor 30% Preterm premature rupture of the membranes

Pathogenic processes Activation of the maternal or fetal hypothalamic pituitary

axis Infection Decidual hemorrhage Pathologic uterine distention

Pathogenesis

Premature activation Major maternal physical/psychologic stress Stress of uteroplacental vasculopathy Mechanism

Increased Corticotropin-releasing hormone Fetal ACTH Estrogens (incr myometrial gap junctions)

Activation of the HPA Axis

Clinical/subclinical chorioamnionitis Up to 50% of preterm birth < 30 wks GA

Proinflammatory mediators Maternal/fetal inflammatory response Activated neutrophils/macrophages TNF alpha, interleukins (6)

Bacteria Degradation of fetal membranes Prostaglandin synthesis

Inflammation

History: Current and Historical Risk Factors Mechanical

Uterine contractions Home uterine activity monitoring

Biochemical Fetal fibronectin

Ultrasound Cervical length

Prediction of Preterm Delivery

Glycoprotein in amnion, decidua, cytotrophoblast Increased levels secondary to breakdown of the

chorionic-decidual interface Inflammation, shear, movement

Fetal Fibronectin (fFN)

Fetal fibronectin as a predictor for delivery within 7 and 14 days after sampling,

combined results

Delivery <7 days Delivery <14 days

Sensitivity Specificity Sensitivity Specificity (percent), (percent), 95 (percent), 95 (percent), 95 95 percent CI percent CI percent CI percent CI

Study group

All studies 71 (57-84) 89 (84-93) 67 (51-82) 89 (85-94)

Women with

preterm labor 77 (67-88) 87 (84-91) 74 (67-82) .

87 (83-92)

Asymptomatic 63 (26-90)* 97 (97-98) 51 (33-70) .

96 (92-100)(low risk or high-risk) women

CI: confidence interval.* Only one study included in analysis. Fixed-effects model used (homogeneity test P >0.10).

Data from: Leitich, H, Kaider, A. Fetal fibronectin - how useful is it in the prediction of preterm birth? BJOG 2003; 110 (Suppl 20):66.

Fetal fibronectin vs. Clinical assessment

of Preterm Labor Parameter Sensitivity (percent) PPV (percent) NPV (percent)

Fetal fibronectin 93 29 99

Cervical dilatation >1 cm 29 11 94

Contraction frequency 8/h 42 9 94

PPV: positive predictive value; NPV: negative predictive value.Data derived from symptomatic women and reflect the ability to predict delivery within

seven days.

Adapted from: Iams, JD, Casal, D, McGregor, JA, et al. Am J Obstet Gynecol 1995; 173:141.

Transvaginal Reproducible Simple

Sonographic Assessment of Cervical Length

(Dijkstra et al Am J Obstet Gynecol 1999)

Sonographic Assessment of Cervical Length

Sonographic Assessment of Cervical Length

Integration of ….. History Cervical length Fibronectin

Assessment of Risk

Prediction of spontaneous preterm delivery before 35 weeks gestation among asymptomatic low risk women

Adapted from: Iams, JD, Goldenberg, RL, Mercer, BM, et al. Am J Obstet Gynecol 2001; 184:652.

Cervical length < 25 mm (percent)

Fetal fibronectin (percent)

Both tests (percent)

Positive test result

8.5 3.6 0.5

Sensitivity 39 23 16

Specificity 92.5 97 99.5

Positive Predictive Value

14 20 50

Negative Predictive Value

98 98 94.4

History of Delivery 18-26 27-31 32-36 > 37

FFN (-)

CL < 25 25% 25% 25% 6%

CL 26-35 14% 14% 13% 3%

CL > 35 7% 7% 7% 1%

FFN (+)

CL < 25 64% 64% 63% 25%

CL 26-35 46% 45% 45% 14%

CL > 35 28% 28% 27% 7%

Risk of Preterm Birth (< 35 wks)

Clinical Criteria Persistent Ctx 4 q 20 min or 8 q 60 min Cervical change/80% effacement/> 2cm dil.

Among the most common admission Dx Inexact diagnosis: PTL is not PTD

30% PTL resolves spontaneously 50% of hospitalized PTL deliver @ term

Clinical Diagnosis of Preterm Labor

Two goals of management: Detection and treatment of disorders associated with PTL Therapy for PTL itself

Bedrest, hydration, sedation NO evidence to support in the literature

Management of Preterm Labor

Evaluation of Patient in Suspected PTL• Prompt eval is critical• Fetal heart monitor – to help quntify frequency and duration of

contractions• Determine status of cervix – visual inspection with speculum*

– *perform first if suspected ROM b/c digital exam may increase the risk of infection in the setting of PROM

• UA and urine culture• Rectovaginal swab for GBS• Gonorrhea and Chlamydia cultures if inidcated by history or PE• Ultrasound exam – assess GA of fetus, cervical length, estimate

amniotic fluid volume, fetal presentation and placental location• Monitor patients for bleeding – placental abruption and previa may be

associated with PTL

OPTIONS FOR MEDICAL MANAGEMENT

Drug Mechanism Efficacy Side Effects Contraindications

Beta adrenergic receptor agonist (terbutaline )

Interferes w/ myosin light chain kinase

Inhibits actin myosin interaction

? 48 hours.

No change in perinatal outcome

Tachycardia, palpitations, hypotension, SOB, pulmonary edema, hyperglycemia

Maternal cardiac disease, uncontrolled diabetes and hyperthyroidism

Magnesium Sulfate

Competes with Calcium at plasma memb (?)

Unproven Diaphoresis, flushing, pulmonary edema

Myasthesthenia gravis, renal failure

Ca Channel Blocker (nifedipine)

Directly block influx of Ca thru cell membrane

Unproven Nausea, flushing, HA, palpitations

Caution: LV dysfunction, CHF

Cyclooxygenase Inhibitors (indomethacin)

Decrease prostaglandin production

Unproven Nausea, GI reflux, spasm fetal DA, oligo

Platelet or hepatic dysfunction, GI ulcerRenal dysfunction, asthma

Recommended for: Preterm labor 24 – 34 weeks PPROM 24 – 32 weeks

Reduction in: Mortality, IVH, NEC, RDS

Mechanism of action: Enhanced maturation lungs Biochemical maturation

Antenatal Steroids

Dosage: Dexamethasone 6 mg q 12 h Betamethasone 12.5 mg q 24 h

Repeated doses - NO Effect:

Within several hours Max @ 48 hours

Antenatal Steroids

17 alpha OH Progesterone Women with prior PTB (singleton) 24 – 26 wks (16 – 20 wks) – 36 weeks

Reduces the risk of recurrent preterm birth < 37 wks 36% vs 55% < 35 wks 21% vs 31% < 32 wks 11% vs 20%

Progesterone for History of PTB

A 36 year old black female G2 P 0101 presents at 8 weeks gestation.

History: Chronic hypertension, no meds Smokes 1 ppd, Drugs (-) ETOH (+) STI – history of chlamydia, HIV positive Surgical history : LEEP, tubal ligation

Case #1

Bottom Line Concepts Preterm labor - “Regular” uterine contractions, with cervical

“change” or > 2 cm dilation or > 80% effacement, occurring before 37 weeks

There are numerous risk factors – both modifiable and non-modifiable. Counsel patients regarding ways to reduce their modifiable risk factors

Clinical assessment of risk includes consideration and evaluation of history, cervical length and fetal fibronectin

There are a variety of tocolytic drugs available, though most have unproven efficacy

Antenatal steroids are recommended for: Preterm labor 24 – 34 weeks and PPROM 24 – 32 weeks

References and Resources

APGO Medical Student Educational Objectives, 9th edition, (2009), Educational Topic 24 (p50-51).

Beckman & Ling: Obstetrics and Gynecology, 6th edition, (2010), Charles RB Beckmann, Frank W Ling, Barabara M Barzansky, William NP Herbert, Douglas W Laube, Roger P Smith. Chapter 20 (p201-205).

Hacker & Moore: Hacker and Moore's Essentials of Obstetrics and Gynecology, 5th edition (2009), Neville F Hacker, Joseph C Gambone, Calvin J Hobel. Chapter 12 (p146-150).