Preterm Labor Presentation for Emory University Hospital Midtown.

1. CHUKWUMA I. ONYEIJE, MD
ATLANTA PERINATAL ASSOCIATES
TUESDAY, APRIL 22, 2014
PRETERM BIRTH:
MODERN MANAGEMENT

2. Polling Courtesy of Poll Everywhere.
 To participate in polling for this lecture:
 1. Navigate to: http://pollev.com/onyeije
OR
 2. Text the applicable CODE to:
1-747-444-3548

3. Can You See this Poll Question?

4. What is the percentage of preterm deliveries
in the US (all patients)?

5. What percentage of African American infant are born premature?

6. What has been the trend in preterm delivery in the last 6 years?

7. What is a Preterm birth
 Any birth occurring before 37 weeks’ gestation
 Subdivisions of Preterm birth:
 Late preterm birth (34 to 36 weeks)
 Early preterm (<34 weeks)
 Very preterm (<32 weeks)
 Extremely preterm (<28 weeks)

8. What is a Preterm birth
 Any birth occurring before 37 weeks’ gestation
 Subdivisions of Preterm birth:
 Late preterm birth (34 to 36 weeks)
 Early preterm (<34 weeks)
 Very preterm (<32 weeks)
 Extremely preterm (<28 weeks)

9. Prematurity Risks
 Leading cause of infant death.
 36% of infant deaths in 2005
 Preterm infants are more likely to suffer:
 Neurologic impairment
 Chronic lung disease
 Cerebral palsy
 Developmental delay

10. Prematurity Risks
 Leading cause of infant death.
 36% of infant deaths in 2005
 Preterm infants are more likely to suffer:
 Neurologic impairment
 Chronic lung disease
 Cerebral palsy
 Developmental delay

11. What has happened since 2006?

12. Prior to 2006, the U.S. preterm birth rate had
been steadily rising for more than two decades

13. Since 2006,
~176,000 FEWER
babies have been born preterm
This improvement in the preterm birth rate
has saved $9 billion
in health and societal costs.

14. 2006 - 2012
The Trend in Preterm Birth
 The US preterm birth rate DROPPED for the
SIXTH consecutive year in 2012
Currently 11.5 %
 This represents a 15-year LOW.
 US preterm birth rate PEAKED in 2006 at 12.8 %

15. The Trend in Preterm Birth
2006 – 2012
Racial disparities.
• Preterm birth rate African-American infants is the
LOWER THAN IT HAS BEEN IN 20 YEARS
• African-American preterm birth rate is now 16.8%.
Down from 18.5% in 2006; BUT…
• Remains the highest of all racial groups.

16. Our nations preterm birth rate is still the
HIGHEST
rate of preterm birth of
any industrialized country.

17. Preterm Birth By Country
0 5 10 15 20
Papua New Guinea
Sierra Leone
Bangladesh
Malawi
Russia
Brazil
Turkey
Malaysia
Japan
United Kingdom
Germany
United States
Worldwide Average
Worldwide Low Income Middle Income High Income
Source: http://www.nature.com/news/pre-term-births-on-the-rise-1.10556

18. March of Dimes 2013 Preterm Delivery Report
Card Results.
Source: http://www.marchofdimes.com/mission/prematurity-reportcard.aspx

19. Why have preterm births DECREASED?
?

20. Does prenatal care improve
pregnancy outcome?

21. ANSWER:
YES AND NO.
Does prenatal are improve
pregnancy outcome?

22. Does prenatal care improve pregnancy outcome.
 YES:
 Lower risk of preterm delivery among patients with ANY kind
of prenatal care than NO prenatal care.
 BUT:
 This is NOT related to the kind of prenatal care provided.
 Behrman RE, Stith Butler A. Committee on understanding premature birth and assuring
healthy outcomes: causes, consequences, and prevention. Washington, DC: National
Academies Press, 2007

23. What DOES NOT seem to work…
 Treating nutritional deficiencies
 Vitamin C, Vitamin E, Calcium, n-3 fatty acids.
 Treating genitial tract microorganisms.
 Treating periodontal disease
Iams et al, NEJM; 370;3 nejm.org january 16, 2014

24. What DOES seem to work?
 Fewer uninsured women
 37 states reduced the percentage of uninsured women of
childbearing age
 Less smoking
 35 states reduced the percentage of women of childbearing age
who smoke
 Fewer late preterm births
 28 states lowered the late preterm birth rate (infants born
between 34 and 36 weeks gestation).
Source: http://www.marchofdimes.com/mission/prematurity-reportcard.aspx

25. Centers for Disease Control and Prevention. Youth
tobacco surveillance-United States, 1998-1999.
Morbidity and Mortality Weekly Report .
2000b;49(SS10):1–94

26. What DOES seem to work?
 Increased interpregnancy intervals
 Better IVF
 Progesterone therapy
 Cervical cerclage
Iams et al, NEJM; 370;3 nejm.org january 16, 2014

27. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1508292/pdf/amjph00020-0040.pdf

28. Interpregnancy Interval
 Shorter time for repletion of maternal nutrient stores.
 Reduction in adverse birth outcomes.
 Pre-term infant
 Small for gestational age infant
 Neonatal death.

29. Other Risk Factors:
 Tobacco use
 Dose-dependent increase in the risk of preterm birth
 Substance abuse
 Short cervix
 Cervical surgery
 Uterine malformation
 Large (> 5cm) uterine fibroids
 Moderate to severe anemia in the first trimester
 Fetal factors
 Growth restriction
 Congenital anomalies
 Male gender

30. Risk Factors for Preterm Birth
 Previous preterm birth
 Short interpregnancy interval
 Assisted reproduction
 Multifetal gestation
 Decidual hemorrhage
 Infection and inflammation
 Asymptomatic bacteriuria
 Maternal periodontal disease

31. Previous preterm birth
 Strongest risk factor for future preterm delivery
 Data from McManemy et al:
 One preterm birth: 14-22 % risk.
 Two preterm births: 28 -42%
 Three or more: Up to 75%
 A term birth decreases the risk of preterm birth in
subsequent pregnancies
(McManemy et al, 2007)

32. RECALL
0 5 10 15 20
Papua New Guinea
Sierra Leone
Bangladesh
Malawi
Russia
Brazil
Turkey
Malaysia
Japan
United Kingdom
Germany
United States
Worldwide Average
Worldwide Low Income Middle Income High Income

33. 0 20 40 60 80
THREE PREVIOUS PTD
TWO PREVIOUS PTD
ONE PREVIOUS PTD
United States
Worldwide Average
Worldwide
PTD X 3
PTD X 2
PTD X 1
Averages
Source: McManemy J., Cooke E., Amon E., Lee T.: Recurrence risk for
preterm delivery. Am J Obstet Gynecol 2007; 196(6):576.e6-e7

34. Current Understanding:
Pathology Underlying
Preterm Labor

35. Reversal of Progesterone to Estrogen Activity
 Actions of progesterone
 Inhibits cervical ripening
 Reduces myometrial contractility
 Reduces oxytocin receptor synthesis
 Reduces oxytocin receptor function

36. Progesterone Levels
Normal vs. Threatened prematurity

37. Pathophysiologic Mechanisms for
Prematurity
Activation of
Maternal/Fetal
HPA Axis
 Maternal/Fetal
stress
Inflammation/
Infection
 Chorio-decidual
 Systemic
Decidual
Hemorrhage
 Abruption
Pathological Uterine
Distension
 Multifetal pregnancy
 Polyhydramnios
 Uterine abnormality
Preterm Birth
Lockwood CJ, Kuczynski E. Paediatric Perinat Epidemiol. 2001;15(suppl 2):78-89.
Estimated at 40%Estimated at 30% Estimated at 20% Estimated at 10%

38. Premature Decidual Activation
Campbell S. Ultrasound Obstet Gynecol 2011
• Occult upper genital tract infection
• Release of proinflammatory cytokines in the cervix
• Release of proinflammatory cytokines at the
choriodecidual interface
•  Cervical softening and effacement

39. Pathophysiologic Mechanisms for
Prematurity
Activation of
Maternal/Fetal
HPA Axis
 Maternal/Fetal
stress
Inflammation/
Infection
 Chorio-decidual
 Systemic
Decidual
Hemorrhage
 Abruption
Pathological Uterine
Distension
 Multifetal pregnancy
 Polyhydramnios
 Uterine abnormality
Preterm Birth
Lockwood CJ, Kuczynski E. Paediatric Perinat Epidemiol. 2001;15(suppl 2):78-89.
Estimated at 40%Estimated at 30% Estimated at 20% Estimated at 10%

40. Is progesterone our new
“Silver Bullet” ?

41. What is considered a “short” cervix (between 18 to 24 weeks)?

42. 42
“Prevention of Recurrent Preterm Delivery by 17
α-Hydroxyprogesterone Caproate”
 “The NICHD Study”
 Meis, Paul J. et al, N
Engl J Med, June
12, 2003
 (initially presented
SMFM, Feb. 6, 2003)

43. 17 α-hydroxyprogesterone caproate
Approved by FDA February 3, 2011
 Indicated to reduce the risk of preterm birth in women with
a singleton pregnancy who have a history of singleton
spontaneous preterm birth
• MakenaTM
• 17P content: 250 mg/ml
• 5 ml multi-dose vial with preservative

44. 44
Meis et al,
New England Journal of Medicine, 2003
Maternal Outcomes
17P Plac. RR CI
N 306 153
< 37 w 36.3% 54.9% 0.66 .54 - .81
< 35 w 20.6% 30.7% 0.67 .48 - .93
< 32 w 11.4% 19.6% 0.58 .37 - .91

45. 45
Meis et al,
New England Journal of Medicine, 2003
Neonatal Outcomes
Outcome 17P Placebo RR 95% CI
BW < 2500 27.2% 41.1% 0.66 0.51 – 0.87
IVH 1.3% 5.2% 0.25 0.8 – 0.82
NEC 0% 2.6% NA NA
Suppl O2 14.9% 23.8% 0.62 0.42 – 0.92

46. 46
Meis et al,
New England Journal of Medicine, 2003
Study conclusion: “Weekly injections of 17P
resulted in a substantial reduction in the
rate of recurrent preterm delivery among
women who were particularly high risk for
preterm delivery and reduced the
likelihood of several complications in their
infants.”

47. Bibliography of Selected Publications (2007 – 2012)
Data from Women Receiving
Alere 17P Administration Nursing Service (17P-HAS)
• Sibai 2012
• Gonzalez-Quintero 2012
• Timofeev 2012
• Lucas 2012
• Gonzalez-Quintero 2012
• Rebarber 2012
• Timofeev 2012
• Timofeev 2012
• Gonzalez-Quintero 2011
• Unal 2011
• Gonzalez-Quintero 2011
• Coleman 2011
• Barton 2011
• Gonzalez-Quintero 2011
• Gonzalez-Quintero 2011
• Rittenberg 2011
• Gonzalez-Quintero 2010
• Joy 2010
• Rebarber 2010
• O’Brien 2009
• Eggerman 2009
• Eggerman 2009
• Page 2009
• Rittenberg 2009
• Rittenberg 2008
• Ventolini 2008
• Rebarber 2008
• Guzman 2007
• Rittenberg 2007
• How 2007
• Rebarber 2007
• Rebarber 2007
• Gonzalez-Quintero 2007
47

48. 48
17P: Side Effects and Precautions
Precautions
 Discontinue if thrombosis or thromboembolism
occurs
 Consider discontinuing if allergic reactions occur
 Decreased glucose tolerance: Monitor pre-diabetic
and diabetic women
 Fluid retention: Monitor women with conditions that
may be affected by fluid retention, such as
preeclampsia, epilepsy, cardiac or renal dysfunction
 Depression: Monitor women with a history of clinical
depression; discontinue if depression recurs
MakenaTM Prescribing Information, Ther-Rx Corporation St. Louis, MO February, 2011

49. 49
Meis et al,
New England Journal of Medicine, 2003
Fetal Safety
 17P appeared to be safe.
 There was no increase in the rate of congenital
anomalies in the progesterone group.
 These results are consistent with surveys of the
literature that have indicated an absence of
teratogenic effects from the use of 17P during
pregnancy.”

50. 50
Progestins and Evidence of Fetal Harm
• Cohort of 988 progestin-exposed (90% 17P or
progesterone; >60%: 17P only)
• Outcomes tabulated included GU, CNS, and CV
anomalies; mean f/u: 11.5 years
• No significant detection of congenital anomalies with
progestin exposure
• (“May not apply to androgenic progestins”)
Resseguie LJ et al. Congenital malformations among offspring exposed in utero to
progestins, Olmsted County, Minnesota, 1936-1974.
Fertility and Sterility 1985;43(4):514-9.

51. 4-year Follow-up Safety Study
 No significant differences were seen in health
status or physical examination, including genital
anomalies, between 17P and placebo children
 Scores for gender-specific roles were within the
normal range and similar between 17 alpha-
hydroxyprogesterone caproate and placebo
groups.
Northen AT. Obstet Gynecol 2007

52. No Evidence of 17P as Unsafe
 Multi-Generational Developmental and
Reproductive Toxicology study
 Developmental and toxicology study in rats
shows no evidence of a safety signal for
hydroxyprogesterone caproate
 Conclusions combined with the results of 11
trials showing fetal loss rates of 3.6% for 17P and
5.1% for placebo
Schardein J. Am J Obstet Gynecol 2012

53. Perinatal Mortality Reassuringly Low
17P (start) ≤18 wk
(n = 3632)
18-20 wk
(n = 1367)
>20/<21 wk
(n = 494)
p
Stillbirth 6 (0.2%) 1 (0.1%) 1 (0.2%) 0.705
Miscarriage 10 (0.3%) 3 (0.2%) NA 0.492
NN death 18 (0.5%) 4 (0.3%) 3 (0.6%) 0.554
Total PNM 34 (0.9%) 8 (0.6%) 4 (0.8%) 0.478
53
Sibai Am J Perinatoll 2012

54. 17P: Contraindications
• Current or history of thrombosis or
thromboembolic disorders
 Known or suspected breast cancer, other
hormone-sensitive cancer, or history of these
conditions
 Undiagnosed abnormal vaginal bleeding
unrelated to pregnancy
 Cholestatic jaundice of pregnancy
 Liver tumors, benign or malignant, or active liver
disease
 Uncontrolled hypertension
MakenaTM Prescribing Information, Ther-Rx Corporation St. Louis, MO February, 2011

55. 17P and Risk for Gestational Diabetes
p-value OR (95% CI)
17OHPC initiated
at 16-20 weeks
0.025 1.67 (1.07, 2.63)
17OHPC initiated
at 21-24 weeks
0.515 1.22 (0.66,2.26)
Maternal age ≥ 35
years
0.001 2.11 (1.37,3.25)
Morbid obesity >
39.9 kg/m2
0.063 1.60 (0.97,2.63)
Eggerman R Am J Obstet Gynecol 2009

56. Cerclage Placement
Your text here

57. Cerclage: Controversies and Certainties
 J. Owen et al, AmJOBG, 2009:
 Randomized trial
 Previous early preterm birth AND Cervix < 2.5 cm.
 Outcome: Birth at less than 35 weeks.
 Observation vs. Cerclage
 Cervix < 2.5 cm: NO BENEFIT
 Cervix < 1.5 cm: BENEFIT

58. Cerclage: Controversies and Certainties
 Berghella et al, Obstet Gynecol, 2011.
 Metaanalysis of 5 trials
 Cerclage for short cervix < 2.5 cm
 CERCLAGE EFFECTIVE
 Relative risk, 0.70
 Confidence interval: 0.55 – 0.89

59. Cerclage: Caution
 The large trials for women with a short cervix were
designed and performed BEFORE progestogens were
used for that indication.
 Available studies suggest vaginal progesterone and
cervical cerclage are SIMILARLY effective in
reducing the risk of preterm birth among high risk
women.

60. Cerclage: Caution
There have been NO studies
to directly compare cerclage
and progesterone to date.

61. Progesterone vs. Cerclage
Current recommendations…
 Short cervix who have
NO previous preterm birth
 Previous preterm birth.
 For women with a previous
preterm birth AND a short
cervix.
 Supplemental cerclage for
short cervix and NO
previous preterm birth?
Vaginal progesterone
17- alpha
hydroxyprogesterone
Cervical cerclage
NO DATA
Am J Obstet Gynecol 2012;206:376-86.
ACOG practice bulletin no. 130: Obstet
Gynecol. 2012;120:964-73

62. Iams et
al,
NEJM
January
16, 2014

63. Comprehensive obstetrical history
Ultrasound confirmation of EGA and
number of fetuses
Initial prenatal visit

64. History of spontaneous preterm
birth OR stillbirth before
24 wk presenting as
labor, SROM or advanced
dilation?
Prescribe 17-
OHP, 250 mg IM
weekly from 16 to 37
weeks
Yes No
Is this a singleton
pregnancy?

65. History of spontaneous preterm
birth OR stillbirth before
24 wk presenting as
labor, SROM or advanced
dilation?
Prescribe 17-
OHP, 250 mg IM
weekly from 16 to 37
weeks
Yes

66. Prescribe 17- OHP, 250 mg IM
weekly from 16 to 37 weeks
Measure TVCL every 14 days
from 16–24 wk of
gestation, every 7 days if CL
<30 mm
History of preterm birth:
If TVCL <25 mm before24 wk of gestation:
1. Consider CERCLAGE
(especially if patient had prior spontaneous preterm
birth at <28 wk or if membranes are visible)
2. Continue progesterone

67. Is there a history of
spontaneous preterm birth or
stillbirth before
24 wk presenting as labor,
SROM or advanced dilation?
No
Is this a singleton
pregnancy?
No previous preterm birth

68. Is this a singleton
pregnancy?
Signs or symptoms
of PTL ?
(e.g., persistent pelvic pressure,
cramps, spotting or vaginal
discharge)?
Progestogens are ineffective
and cerclage may increase
the risk of preterm birth
Singleton vs. Multiple Gestation

69. Singleton Pregnancy, WITH symptoms of preterm labor
Signs or symptoms
of PTL ?
(e.g., persistent pelvic
pressure, cramps, spotting or vaginal
discharge)?
Have TVCL
performed by
credentialed
ultrasonographer
Next
Slide
YES

70. Singleton Pregnancy, NO symptoms of preterm labor
Signs or symptoms
of PTL ?
(e.g., persistent pelvic pressure,
cramps, spotting or vaginal discharge)?
Use one of the following site-
specific screening strategies.
(S4)

71. Site-specific screening
strategies.
(S4)
Universal TVCL screening at 18–24 wk
Universal TACL screening at 18–24 wk of gestation, until CL <35 mm
Selective TVCL screening of women with the following risk factors:
Prior preterm birth at <34 wk with unknown cause, or twins
History of genitourinary infection
Conception with fertility drugs
Black race
Previous cervical surgery
BMI <19.6 or >35.0
Periodontal disease

72. Signs or symptoms
of PTL ?
(e.g., persistent pelvic
pressure, cramps, spotting or vaginal
discharge)?
The patient with “Symptomatic” preterm labor.
Have TVCL
performed by
credentialed
ultrasonographer

73. The Clinical
Evaluation of
Preterm
Labor

74. Diagnosis of Preterm Labor
 Difficult.
 “Regular painful uterine contractions AND cervical dilatation
or effacement at a preterm gestational age”
 Half of women HOSPITALIZED for preterm labor
deliver at TERM.
 Regardless of therapy.
• Signs and symptoms of preterm labor
• Cramping
• Back pain
• Contractions
• Bloody show

75. Tocodynamometry
to evaluate for the
presence of uterine
contractions

76. Speculum exam
to assess for
ruptured
membranes or
bleeding

77. Initial laboratory
evaluation
urinalysis & culture
urine toxicology
GBS culture

78. FFN testing
 High negative predictive value
 More than 99% of symptomatic patients with a
negative fFN did not deliver within 14 days
 Cannot be performed with:
 Vaginal bleeding
 Ruptured membranes
 After recent intercourse
 After vaginal examination
 After transvaginal ultrasound

79. ONYEIJE’S
3, 2, 1 PRINCIPLE
Management of a Short Cervix

80. Iams J. N Engl J Med 1996

81. 0 5 10 15 20 25
Cervix ~ 1.9 cm
Cervix ~ 2.0 - 3.0 cm
Cervix > 3.0 cm
United States
Worldwide Average
Worldwide
CVX ~ 1.0 cm
CVX ~ 2 - 3 cm
CVX ~ 3.0 cm
Averages
Source: The Length of the Cervix and the Risk of Spontaneous Premature Delivery. Jay D.
Iams, M.D., Robert L. Goldenberg, M.D., et al. N Engl J Med 1996; 334:567-573February 29, 1996
Probability of Delivery before 32 weeks
Based on Cervical Length before 24 weeks.

82. Cervical Length Triage for Preterm Labor
Cervical Length
< 1.9 cm
High
Risk
2.0 to 2.9 cm
Increased
Risk
> 3.0 cm
Low
Risk

83. Normal Cervix

84. Low Risk (> 3.0 cm)
 LOW risk of preterm birth.
 FFN testing NOT mandatory.
 Observe for 4 to 6 hours to confirm fetal well-being.
 Reactive nonstress test
 Rule out abruption
 Rule out Infection.
 Rule out Cervical change
 Arrange follow-up in one to two weeks
 Give PTL instructions
 Bleeding, rupture of membranes, decreased fetal activity

85. Increased Risk (2.0 to 3.0 cm)

86. Increased Risk (2.0 to 3.0 cm)
 Most of these women do NOT deliver preterm.
 FFN testing indicated.
 If FFN positive  See High Risk Slide.
 If FFN negative  See Low Risk Slide.

87. High Risk

88. The spectrum of cervical anatomy

89. High Risk
 High risk of preterm birth
 Regardless of the fFN result
 Active management recommended
 Prevention of morbidity associated with
preterm birth.

90. Management of Preterm Labor
 Betamethasone
 Vaginal progesterone
 Tocolysis for up to 48 hours.
 GBS Chemoprophylaxis
 Antibiotics for UTI
 Magnesium sulfate for neuroprotection
 Between 24 and 32 weeks.

91. Summary
 Preterm birth remains a leading cause of infant
death in the United States, especially among African
Americans.
 Changes in IVF and reductions in scheduled births
before 39 weeks have resulted in decreased preterm
birth rates.

92. Summary
 Strategies to identify and treat medical risk factors in
early pregnancy have NOT been effective in reducing
preterm birth rates.
 Previous preterm birth and a short cervix (≤20
mm, as measured by transvaginal ultrasonography)
are major risk factors for preterm birth.

93. Summary
 The use of progesterone supplementation in women
with a previous preterm birth, a short cervix, or both
was shown in randomized trials to reduce the
frequency of preterm birth and is recommended for
women with these risk factors.
 Cervical cerclage reduces the risk of recurrent
preterm birth among women with a short cervix.

94. Thank you.

95. Periodontal Disease
 Increases the risk of preterm labor and low birth weight.
 Proposed mechanism:
 Seeding of the placenta or amniotic fluid by oral pathogens and
systemic inflammation.
 Oral bacteria associated with an increased risk of preterm delivery:
 Bacteroides forsythus
 Porphyromonas gingivalis
 Actinobacillus actinomycetemcomitans
 Treponema denticola
 Fusobacterium nucleatum
Offenbacher S., Jared H.L., O’Reilly P.G., et al: Potential pathogenic mechanisms of periodontitis
associated pregnancy complications. Ann Periodontol 1998; 3(1):233-250.

96. Periodontal Disease
 Nonsurgical treatment of periodontal disease was
NOT effective in reducing preterm births, low birth
weight, or growth restriction.

Michalowicz B.S., Hodges J.S., DiAngelis A.J., et al: Treatment of periodontal disease
and the risk of preterm birth. N Engl J Med 2006; 355(18):1885-1894.

97. Genital Infections
Associated with preterm birth
Causality has not been proved
Treatment for genital infections is often indicated, but
has NOT been shown to reduce the risk of preterm
birth.

98. Preterm labor itself is NOT an
indication for antibiotics in the
absence of:
Documented infection
or
GBS prophylaxis

99. GBS CHEMOPROPHYLAXIS (< 37 WEEKS)

100. Repeat Doses of Steroids?
 Administering a repeat course of therapy reduces the
risk of respiratory distress syndrome (RDS).
 Repeat doses of prenatal corticosteroids for women at
risk of preterm birth for improving neonatal health
outcomes.Cochrane Database Syst Rev. 2011 Jun
15;(6):CD003935. doi: 10.1002/14651858.CD003935.pub3.
 This study did NOT evaluate the RISKS of repeat
doses of steroids…

101. Repeat Dose Controversies
 In the Maternal Fetal Medicine Units network (MFMU)
trial, 63 percent of patients received 4 or more courses of
therapy.
 These patients had:
 More IUGR < 10th percentile
 More IUGR < 3rd percentile
 Smaller placenta size
 (?) Increased risk of cerebral palsy.
 5 cases vs 1 case.
 REFERENCE:
 Am J Obstet Gynecol. 2006 Sep;195(3):633-42. Epub 2006 Jul 17.
 Single versus weekly courses of antenatal corticosteroids:
evaluation of safety and efficacy.

102. Repeat Dose Controversies
 A small prospective cohort study reported lower
measures of attention and speed in adolescence and
young adults exposed in utero to multiple courses of
antenatal corticosteroid therapy.

103. Rescue Dose Steroids
 In 2011 and 2012, the American College of
Obstetricians and Gynecologists (ACOG)
endorsed the concept of a SINGLE course of rescue
steroids in women who remain at risk of preterm
delivery
 These publications recommend AVOIDING regularly
scheduled repeat courses or more than two courses
of antenatal corticosteroids.
 ACOG Committee Opinion No. 475: Antenatal
corticosteroid therapy for fetal maturation.

104. Indications for Rescue Dose Steroids
 Patient at high risk for delivery within the next 7
days
 Initial course of antenatal corticosteroids at <28
weeks of gestation
 Prior exposure to antenatal corticosteroids at least
two weeks earlier