Slide 1 - UNC School of Medicine

							Preterm Labor and Delivery
           UNC School of Medicine
      Obstetrics 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
          Definition: Preterm Labor

 “Regular” uterine contractions
 With
   Cervical “change” or
   > 2 cm dilation or
   > 80% effacement
               Preterm Delivery

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

 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!
     Leading Causes of Neonatal Death (USA)

                                                                           Neonatal    Percentage of
                                                                            deaths    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.
                       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
Infant Mortality
Infant Morbidity
Infant Morbidity
              Risk Factors for Preterm Birth

Non-modifiable                            Modifiable
Prior preterm birth                       Cigarette smoking
African-American race                     Substance abuse
Age <18 or >40 years                      Absent prenatal care
Poor nutrition/low pre-pregnancy weight   Short interpregnancy intervals
Low socioeconomic status                  Anemia
Cervical injury or anomaly                Bacteriuria/urinary tract infection
Uterine anomaly or fibroid                Genital infection
Premature cervical dilatation (>2 cm)     ? Strenuous work
or effacement (>80 percent)               ? High personal stress
Over distended uterus (multiple
  pregnancy, polyhydramnios)
? Vaginal bleeding
? Excessive uterine activity
               Risk Factors for Preterm Birth

Stress                                       Cervical factors
 Single women                                History of second trimester abortion
 Low socioeconomic status                    History of cervical surgery
 Anxiety                                     Premature cervical dilatation or
 Depression                                    effacement
 Life events (divorce, separation, death)   Infection
 Abdominal surgery during pregnancy          Sexually transmitted infections
Occupational fatigue                          Pyelonephritis
 Upright posture                             Systemic infection
 Use of industrial machines                  Bacteriuria
 Physical exertion                           Periodontal disease
 Mental or environmental stress             Placental pathology
Excessive or impaired uterine distention      Placenta previa
 Multiple gestation                          Abruption
 Polyhydramnios                              Vaginal bleeding
 Uterine anomaly or fibroids
 Diethystilbesterol
              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)
             Prediction/Recurrence


 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
                     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
             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)
                     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)
 Bacteria
   Degradation of fetal membranes
   Prostaglandin synthesis
         Prediction of Preterm Delivery

 History: Current and Historical Risk Factors
 Mechanical
    Uterine contractions
    Home uterine activity monitoring
 Biochemical
    Fetal fibronectin
 Ultrasound
    Cervical length
             Fetal Fibronectin (fFN)

 Glycoprotein in amnion, decidua, cytotrophoblast
 Increased levels secondary to breakdown of the
  chorionic-decidual interface
 Inflammation, shear, movement
                 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.
Sonographic Assessment of Cervical Length

 Transvaginal
 Reproducible
 Simple
 Sonographic Assessment of Cervical Length




(Dijkstra et al Am J Obstet Gynecol 1999)
Sonographic Assessment of Cervical Length
              Assessment of Risk

 Integration of …..
   History
   Cervical length
   Fibronectin
   Prediction of spontaneous preterm delivery before 35 weeks
         gestation among asymptomatic low risk women


                                    Cervical length < 25 mm                Fetal fibronectin    Both tests
                                           (percent)                          (percent)         (percent)
        Positive test                              8.5                              3.6            0.5
        result
        Sensitivity                                39                                23            16
        Specificity                               92.5                               97           99.5
        Positive                                   14                                20            50
        Predictive Value
        Negative                                   98                                98           94.4
        Predictive Value




Adapted from: Iams, JD, Goldenberg, RL, Mercer, BM, et al. Am J Obstet Gynecol 2001; 184:652.
  Risk of Preterm Birth (< 35 wks)

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%
      Clinical Diagnosis of 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
         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
    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    Interferes w/        ? 48 hours.    Tachycardia,         Maternal cardiac
receptor agonist   myosin light chain                  palpitations,        disease, uncontrolled
                   kinase               No change in
(terbutaline )                          perinatal      hypotension, SOB,    diabetes and
                   Inhibits actin       outcome        pulmonary            hyperthyroidism
                   myosin interaction                  edema,
                                                       hyperglycemia

Magnesium          Competes with     Unproven          Diaphoresis,    Myasthesthenia gravis,
Sulfate            Calcium at plasma                   flushing,       renal failure
                   memb (?)                            pulmonary edema


Ca Channel         Directly block       Unproven       Nausea, flushing,    Caution: LV
Blocker            influx of Ca thru                   HA, palpitations     dysfunction, CHF
(nifedipine)       cell membrane


Cyclooxygenase     Decrease             Unproven       Nausea, GI reflux,   Platelet or hepatic
Inhibitors         prostaglandin                       spasm fetal DA,      dysfunction, GI ulcer
(indomethacin)     production                          oligo                Renal dysfunction,
                                                                            asthma
                  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
                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
        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
    < 37 wks 36% vs 55%
    < 35 wks 21% vs 31%
    < 32 wks 11% vs 20%
                         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
                     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).