Preterm Labor and Delivery

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Preterm Labor and Delivery

• UNC School of Medicine
• Obstetrics and Gynecology Clerkship
• Case Based Seminar Series

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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

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Definition Preterm Labor

• Regular uterine contractions
• With
• Cervical change or
• gt 2 cm dilation or
• gt 80 effacement

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Preterm Delivery

• Preterm birth lt 37completed weeks
• Very Preterm birth lt 32 weeks
• Extremely Preterm birth lt 28 weeks

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Incidence

• 12.5 USA (2004)
• 2 lt 32 weeks
• Fetal growth
• Small for gestational age lt 10th for GA
• Birthweight
• Low BWT lt 2500 grams
• Very low BWT lt 1500 grams
• Extremely low BWT lt 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 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.
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Significance

• Infant mortality
• Over 50 of infant deaths occur among the 1.5
  infants lt 1500 grams
• 70 of infant deaths occur among the 7.7 of
  infants lt 2500 grams
• Morbidity
• 60 26 weeks
• 30 30 weeks

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Infant Mortality
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Infant Morbidity
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Infant Morbidity
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Risk Factors for Preterm Birth

Non-modifiable
Prior preterm birth
African-American race
Age lt18 or gt40 years
Poor nutrition/low pre-pregnancy weight
Low socioeconomic status
Cervical injury or anomaly
Uterine anomaly or fibroid
Premature cervical dilatation (gt2 cm) or effacement (gt80 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 pregnancy
• Occupational 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 (lt18 or gt40)
• African-American race
• Poor nutrition and low body mass index
• Inadequate prenatal care
• Anemia (hemoglobin lt10 g/dL)
• Excessive uterine contractility
• Low level of educational achievement
• Genotype
• Fetal factors
• Congenital anomaly
• Growth restriction

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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)

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Prediction/Recurrence

• Prior PTD _at_ (23-27 wks) 27
• Prior PPROM 13.5

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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
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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 ACTH
• Estrogens (incr myometrial gap junctions)

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Inflammation

• Clinical/subclinical chorioamnionitis
• Up to 50 of preterm birth lt 30 wks GA
• Proinflammatory mediators
• Maternal/fetal inflammatory response
• Activated neutrophils/macrophages
• TNF alpha, interleukins (6)
• Bacteria
• Degradation of fetal membranes
• Prostaglandin synthesis

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Prediction of Preterm Delivery

• History Current and Historical Risk Factors
• Mechanical
• Uterine contractions
• Home uterine activity monitoring
• Biochemical
• Fetal fibronectin
• Ultrasound
• Cervical length

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Fetal Fibronectin (fFN)

• Glycoprotein in amnion, decidua, cytotrophoblast
• Increased levels secondary to breakdown of the
  chorionic-decidual interface
• Inflammation, shear, movement

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

• Delivery lt7 days
  Delivery lt14 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
  gt0.10).

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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 gt1 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 173141.

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Sonographic Assessment of Cervical Length

• Transvaginal
• Reproducible
• Simple

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Sonographic Assessment of Cervical Length

• (Dijkstra et al Am J Obstet Gynecol 1999)

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Sonographic Assessment of Cervical Length
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(No Transcript)
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(No Transcript)
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Assessment of Risk

• Integration of ..
• History
• Cervical length
• Fibronectin

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

• Adapted from Iams, JD, Goldenberg, RL, Mercer,
  BM, et al. Am J Obstet Gynecol 2001 184652.

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Risk of Preterm Birth (lt 35 wks)
History of Delivery 18-26 27-31 32-36 gt 37
FFN (-)
CL lt 25 25 25 25 6
CL 26-35 14 14 13 3
CL gt 35 7 7 7 1
FFN ()
CL lt 25 64 64 63 25
CL 26-35 46 45 45 14
CL gt 35 28 28 27 7
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Clinical Diagnosis of Preterm Labor

• Clinical Criteria
• Persistent Ctx 4 q 20 min or 8 q 60 min
• Cervical change/80 effacement/gt 2cm dil.
• Among the most common admission Dx
• Inexact diagnosis PTL is not PTD
• 30 PTL resolves spontaneously
• 50 of hospitalized PTL deliver _at_ term

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Management 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

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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

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Options for medical management
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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 ulcer Renal dysfunction, asthma
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Antenatal Steroids

• 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

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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 _at_ 48 hours

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Progesterone for History of PTB

• 17 alpha OH Progesterone
• Women with prior PTB (singleton) 24 26 wks
• (16 20 wks) 36 weeks
• Reduces the risk of recurrent preterm birth
• lt 37 wks 36 vs 55
• lt 35 wks 21 vs 31
• lt 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 ()
• STI history of chlamydia, HIV positive
• Surgical history LEEP, tubal ligation

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Bottom Line Concepts

• Preterm labor - Regular uterine contractions,
  with cervical change or gt 2 cm dilation or gt
  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

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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).