Sequelae of Preterm Birth

1
Sequelae of Preterm Birth
(75)
Perinatal Mortality
(10)
(50)
Neurologic Handicap
2
Incidence of Preterm Birth in The
U.S.A.1981-1994
3
Time Trends in Low Birth Weight (lt1,500 g) by
Race/Ethnicity - United States, 1970-1990
4
Increase in Preterm Birth

• 1. Multiple births 2 assisted reproductive
  techniques.
• 2. Increased indicated preterm deliveries.
• 3. Increased spontaneous preterm births ?
  chorioamnionitis.

5
UAB Infants with Birthweights 1000 Grams

• Mean BW Survival
• 1975 900 gms 17
• 1980 860 gms 48
• 1985 820 gms 56
• 1990 804 gms 74

6
Distribution of Neonatal Mortality

• BWT (gms) Distribution
• lt1000 60
• 1000-2500 20
• gt2500 20

Majority associated with congenital anomalies
7
Preterm Birth

• Success Reduction in mortality
• Failures No reduction in SPB
• Little or no reduction in long-term handicap
  among smallest survivors

8
What Outcomes Do We Really Care About?

• Living or dying (mother or fetus/infant)
• Long-term handicap (cerebral palsy)
• Severe neonatal morbidity (high cost)

9
Etiology of Preterm Birth
Preterm Birth for Maternal or Fetal Indications
Spontaneous Preterm Labor
20
50
30
Premature Rupture of Membranes
10
Two Possible Strategies to Improve Low
Birthweight Outcomes

• Prevent low birthweight
• Prevent morbidity and mortality in low
  birthweight fetuses and newborns

11
REVIEW OF INTERVENTIONS TO PREVENT PRETERM BIRTH
Commonly used interventions which have not been
shown to reduce preterm birth include

• Prenatal care
• Risk screening
• Nutrition counseling
• Caloric supplementation
• Protein supplementation
• Iron supplementation
• Most labor inhibiting agents

• Drug, alcohol and tobacco cessation programs
• Bed rest
• Hydration
• Home uterine activity monitoring

12
PRENATAL CARE

• In general,
• 1) the provision of prenatal care to a population
  which had none,
• 2) more prenatal care where there was little, or,
• 3) advanced prenatal care where only routine care
  was available
• has not resulted in a reduction in prematurity

13
VALUE OF PRENATAL CARE

• Substantial decrease in stillbirths
• Substantial decrease in term neonatal mortality
• No or marginal effect on preterm birth rate
• No or marginal effect on very low birthweight
  survival

14
Screening for Risk of Preterm Delivery

• Do the demographic/historical scoring systems
  have any use?

15
Risk Scoring Systems and Preterm Delivery

• Low sensitivity and high false positive rates.
• Most of those who eventually have a preterm birth
  are from the low-risk group, I.e., many false
  negatives.
• Identification of the high-risk status has not
  led to a uniform improvement in outcome.

16
Predicting Preterm Birth

• When formal risk scoring for preterm birth is
  part of standard antenatal care, a large number
  of interventions are applied with a frequency
  that is considerably higher than that found
  elsewhere.
• Chalmers Kierse

17
Bed Rest

• Recommended for
• Treatment of first trimester bleeding
• Treatment of second and third trimester bleeding
• Prevention of PTL in singletons
• Prevention of PTL in twins
• Treatment of PTL
• Prevention of preeclampsia
• Treatment of preeclampsia
• Treatment of non-proteinuric hypertension
• Treatment of edema
• Treatment of growth retardation

18
Bed Rest

• Randomized studies show no improvement in outcome
  associated with bed rest in these conditions
• First trimester bleeding
• Prematurity in twins
• Preeclampsia
• Non-proteinuric hypertension
• Growth retardation
• There are no studies showing benefits of bed rest
  associated with preterm labor.

19
Four randomized studies of bed rest in hospital
in twin gestation to prevent preterm delivery

• Reference Hosp. (wk) Outcome
• Hartikainen-Sorri et al 30 No change
• 1984 (N 146)
• Saunders et al. 32 30 PTD in study subjects
• vs. 19 in controls (p lt 0.05)
• Crowther et al. 34 No change
• 1989 (N139)
• MacLennan et al 26-30 PTD before 32 wk,
• 16 in study subjects
• vs 8 in controls

20
Preterm Labor

• There were no significant differences in the
  outcomes of women randomized in observation,
  hydration, or one dose of subcutaneous
  terbutaline.

(Guinn et al, 1997)
21
Antibiotics in Women with Preterm Labor and
Intact Membranes

• Delayed Improved Infant Study Antibiotic
  N Delivery OutcomeMacGregor, 1986 Erythromycin
  17 Yes No
• Morales, 1988 Erythromycin, Ampicillin 150 Yes
  No
• Winkler, 1988 Erythromycin 19 Yes -
• Newton, 1989 Erythromycin / Ampicillin 95
  No No
• MacGregor, 1991 Clindamycin 103 Yes No
• McCaul, 1992 Ampicillin 40 No No
• Romero, 1993 Ampicillin / Amoxicillin /
  Erythromycin 275 No No
• Cox, 1995 Ampicillin / Amoxicillin 78 No
  No
• Gordon, 1995 Ceftizoximine 117 No No

22
Antibiotics in Women with Preterm Labor and
Intact Membranes

• Meta-analysis of existing RCTs
• These results do not support the routine use of
  antibiotics in women in preterm labor

Egarter et al, 1996
23
Antibiotics and Preterm BirthLabor with Intact
Membranes
Metronidazole and Ampicillin for 6 days at 30
weeks in a RCT

• Study Group Placebo GroupOutcome n43 n38
  
• BWT (x) (g) 2318 2093
• Days to delivery (median) 15 2.5
• Delivery lt7 days () 37 63
• NEC () 0 13 plt.05
• greater prolongation occurred in lt30 week
  pregnancies

Norman et al (South Africa), Br J Obstet
Gynaecol, 1994
24
Antibiotics and Preterm Birth Labor with Intact
Membranes
Ampicillin and Metronidazole for 8 days at 30
weeks in a RCT

• Antibiotics Placebo
• Outcome (n59) (n51) P value
• Days to delivery (x) 48 27 .01
• GA at delivery (wks) (x) 37 34 .01
• Birth lt37 weeks () 42 65 .01
• BWT (g) (x) 2662 2370 .08
• NICU Admission () 40 63 .03
• Neonatal sepsis () 10 22 .18

Svare et al (Denmark), Br J Ob Gyn 1997
25
Survival Curves Cervical Fetal Fibronectin at
Week 24
Proportion not Delivered
1.0
0.9
negative FF
0.8
0.7
0.6
positive FF
30
25
35
Gestational Age
26

• In women with a short cervix, placement of a
  cerclage has produced conflicting data in regard
  to a reduction in preterm birth
• Althuisius and Rust, SMFM 2001

27
FETAL FIBRONECTIN

• A marker for upper genital tract basement
  membrane disruption

28
FFN AND PRETERM BIRTH

• Delivery (weeks) OR
• lt28 60
• lt30 42
• lt32 23
• lt35 11
• lt37 5
• Goldenberg AJOG 1995

29
Summary

• Whether this screening test will ultimately be of
  value in reducing preterm births will depend on
  the availability of an effective intervention.

30
Fetal Fibronectin

• Women in early preterm labor with a negative fFN
  test have lt1 chance of delivering in the next 2
  weeks.
• Use of the test based on its negative predictive
  value may result in fewer hospitalizations and
  reduce cost.

31
Bacterial VaginosisandPreterm Birth

32
BV and Prematurity

• The odds ratio for preterm birth in association
  with BV in nearly every study ranges from 1.5 to
  3.0

33
BV and Prematurity

• Randomized trial of metronidazole and
  erythromycin in women with BV and at high risk
  for PTB
• Rx 23 Placebo 37 p lt.001

Hauth 1994
34
BV and Preterm Birth

• Treating asymptomatic predominantly low-risk
  women with BV with two doses of 2gm of
  metronidazole 48 hours apart, on two occasions
  did not reduce preterm birth.

35

• Advances in molecular biology make possible many
  new predictive tests for preterm birth.
• Predicting preterm birth without an effective
  treatment results in an increase in use of
  ineffective interventions and increased cost, and
  potentially an increase in iatrogenic
  complications.

36
Markers for SPBConsiderations

• The major reason to prospectively identify
  markers of SPB is to identify women who may
  benefit from a specific intervention determined
  to prevent the SPB.
• Before one introduces the use of markers into
  practice, effective intervention in women
  positive for that marker should be available.

37
COCHRANES APHORISM

• Before ordering a test, decide what you will do
  if it is
• 1. Positive 2. Negative
• If both answers are the same, dont do the test.

38
Preventing Prematurity

• Most strategies aimed at preventing preterm birth
  have not been shown to be effective when applied
  to defined populations.
• It is therefore not surprising that the
  prematurity rate has not declined.

39
Can the morbidity and mortality associated with
preterm delivery be reduced or eliminated?

• RDS
• NEC
• IVH
• PDA
• Sepsis
• SIDS

40
ANCS

• In this retrospective analysis, multiple courses
  of antenatal corticosteroids did not improve
  outcome and were associated with increased
  mortality, decreased fetal growth, and prolonged
  adrenal suppression.
• Banks, AJOG 1999

41

• Weekly courses of ANCS did not improve any
  pregnancy outcome compared to a single dose.
• Guinn, SMFM 2001

42

• Everything is a poison.
• The only thing that distinguishes a poison from a
  remedy is dose.
• Alan Jobe

43
Maternal Health Care

• The premature use of new technology pervade
  modern medical practice. Obstetrics, like the
  rest of medicine, must adopt a sensible but
  rigorous approach to the evaluation of new
  technology.
• Thacker

44
Summary

• When resources are limited during pregnancy,
  interventions should be limited to those that
  clearly work.

45
Prematurity

• The treatment of premature labor is identical
  with that already described for term labor, and
  does not require further mention.
• Williams 1908

46

• The great obstacle to discovering the shape of
  the earth, the continents, and the ocean was not
  ignorance but the illusion of knowledge.
• The Discoverers