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Premature Labor

and Delivery

Honor M. Wolfe

Associate ProfessorMaternal Fetal Medicine

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Objectives:

To review the

Definition, frequency and consequence of

preterm delivery

Modifiable and non modifiable risks for

Preterm delivery

Pathogenesis of Preterm delivery

Prediction of Preterm delivery

Management of Preterm labor

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Preterm Labor: Definition

Regular uterine contractions

With

Cervical change or> 2 cm dilation or

> 80% effacement

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Preterm Delivery

- Preterm birth:< 37completed weeks- Very Preterm birth: < 32 weeks

- Extremely Preterm birth: < 28 weeks

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Incidence/Definitions

12.5% USA (2004)

2% < 32 weeks

Fetal growthSmall for gestational age < 10th % for GA

Birthweight:

Low BWT < 2500 gramsVery low BWT < 1500 grams

Extremely low BWT < 1000 grams

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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!

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Leading Causes of Neonatal Death (USA)

Neonatal

deaths

Percentage of

neonatal deaths

Disorders related to prematurity and low birth

weight4,318 23.0

Congenital malformations, chromosomal

abnormalities4,144 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.

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Significance

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

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Risk Factors for Preterm BirthNon-modifiable

Prior preterm birth

African-American race

Age 40 years

Poor nutrition/low prepregnancy 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

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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 stress

Excessive 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

effacement

Infection

Sexually transmitted infections Pyelonephritis

Systemic infection

Bacteriuria

Periodontal disease

Placental pathology

Placenta previa Abruption

Vaginal bleeding

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Risk factors for preterm birth

Miscellaneous

Previous preterm delivery

Substance abuse

Smoking

Maternal age (40)

African-American race

Poor nutrition and low body mass index Inadequate prenatal care

Anemia (hemoglobin

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Prior preterm birth

- Increases risk in subsequent pregnancy

- Risk increases with- more prior preterm births

- earlier GA of prior preterm birth (s)

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Prediction/Recurrence

Prior PTD @ (23-27 wks) 27%

Prior PPROM 13.5%

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FIRSTBIRTH

SECONDBIRTH

SUBSEQUENTPRETERM

BIRTH(%)

Not preterm 4.4Preterm 17.2

Not Preterm Not Preterm 2.6

Preterm Not Preterm 5.7

Not preterm Preterm 11.1

Preterm Preterm 28.4

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Pathogenesis

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

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Activation of the HPA Axis

Premature activation

Major maternal physical/psychologic stress

Stress of uteroplacental vasculopathy Mechanism

Increased Corticotropin-releasing hormone

Fetal ACTHEstrogens (incr myometrial gap junctions)

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Inflammation

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)

BacteriaDegradation of fetal membranes

Prostaglandin synthesis

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Prediction of Preterm Delivery

History: Current and Historical Risk Factors

Mechanical

Uterine contractionsHome uterine activity monitoring

Biochemical

Fetal fibronectin Ultrasound

Cervical length

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Fetal fibronectin as a predictor for delivery

within 7 and 14 days after sampling, combined results

Delivery

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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.

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Sonographic assessment of

cervical length

- Transvaginal- Reproducible

- Simple

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(Dijkstra et al Am J Obstet Gynecol 1999)

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Assessment of Risk:

Integration of

History,Cervical length

Fibronectin

Prediction of spontaneous preterm delivery before 35

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Prediction of spontaneous preterm delivery before 35

weeks gestation among asymptomatic low risk women

Cervical length Fetal fibronectin Both tests

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Risk of Preterm birth < 35 weeks

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%

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Clinical Diagnosis Preterm Labor

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

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Management of Preterm Labor

Bedrest, hydration, sedation

NO evidence to support in the literature

B t d i t i t

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Beta adrenergic receptor agonists

(terbutaline)

Mechanism Interferes w/ myosin light chain kinase

Inhibits actin myosin interaction

Efficacy ? 48 hours. No change in perinatal outcome

Side Effects Tachycardia, palpitations,hypotension,SOB, pulmonary

edema, hyperglycemia

Contraindications Maternal cardiac disease, uncontrolled diabetes and

hyperthyroidism

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Magnesium Sulfate

Mechanism of Action

Competes with Calcium at plasma memb (?)

Efficacy

Unproven

Side Effects

Diaphoresis, flushing, pulmonary edema

Contraindications

Myasthesthenia gravis, renal failure

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Calcium Channel Blockers

Mechanism of Action

Directly block influx of Ca thru cell membrane

Efficacy

Unproven

Side Effects

Nausea, flushing, HA, palpitations

Contraindications

Caution: LV dysfunction, CHF

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Cyclooxygenase Inhibitors

Mechanism of Action

Decrease prostaglandin production

Efficacy

Unproven

Side Effects

Nausea, GI reflux, spasm fetal DA, oligo

Contraindications Platelet or hepatic dysfunction, GI ulcer

Renal dysfunction, asthma

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Antenatal Steroids

Recommended for:

Preterm labor 2434 weeks

PPROM 2432 weeks

Reduction in:

Mortality, IVH, NEC, RDS

Mechanism of action:

Enhanced maturation lungs

Biochemical maturation

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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

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Progesterone for History of PTB

17 alpha OH Progesterone

Women with prior PTB (singleton) 2426 wks

(1620 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%

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Case # 1

A 36 year old black female G2 P 0101

presents at 8 weeks gestation.

History: Chronic hypertension, no meds

Smokes 1 ppd, Drugs (-) ETOH (+)

STIhistory of chlamydia, HIV positive

Surgical history : LEEP, tubal ligation