Preterm, progesterone, SGH

1. Preventing Preterm Labour
Presenter: Dr Lucas Luk
Supervisor: Dr Muniswaran
Sarawak General Hospital O&G Dept
12/9/2012

2. Incidence
Iatrogenic ~20%
PPROM ~20%
Spontaneous preterm labour ~60%
 US ~12.5% (2008)
 UK ~7.6%
 Sarawak General Hospital ~11.1% (2011)

3. Magnitude of Problem
 6.2 billion dollars in hospitalization costs
2010 in US, US2 billion dollars per year of
life thereafter.

4. Epicure/Epicure 2 Studies
 Begain in 1995
 Following Health and outcomes of babies
born before 26wks
 Assessed survival rates, disabilities,
medical complications, motor skills, visual
skills, attention disorders
 Babies assessed at 1 year old, 2/12 yrs
old, 6 yrs old and 11yrs old. (corrected
ages)

5. Gestational Age Survival Rate (1/52) Survival (Discharge)
25wks 75% 55%
24wks 60% 35%
Below 24wks 44% 20%
•314/4004 babies survived and were discharged home
•38% no recorded problems at term (40wks)
•62% had some form of disability:
-Oxygen Dependent (~50%)
-Brain injury (20% with CP)
-Visual problems

6.  1 yr old: 31% with some major motor
problem
 2.5yrs: 48% with some form of
impairment, 4% with significant chest
infections
 6yrs old: 20% no problems
 11yrs old: IQ tests: 45% low scores vs
1.3%; only 39% with no impairment. More
had special needs

7. SGH 2011:
 11.1% Preterm Births
 55% of infant deaths severely preterm
(<34wks)
 No survival <26wks, 700-800g

8. Content
 Primary Prevention
 Secondary Prevention
- Risk Factors
- Screening/Diagnostic Tools
- Management
 Tertiary Prevention
 Conclusion

9. Primary Prevention 1
 Public Education
 Public & Professional Policies
- ART limiting number of embryos transferred
- Minimum paid pregnancy leave
- Workplace hazards, Maximum work week, exemption from
night shift
 Repeated Uterine Instrumentations
 Close Pregnancy (<6/12)
 Substance abuse - Smoking Cessation, coccaine
 Antenatal periodontal care
 Low Socio-Economic status
 Genetics
 Malnutrition (Africa during famines), omega-3,
Zinc
 Extremes of Age

10. EUROPOP
 Working Night Shifts (~50% higher risk)
 Standing >6hrs/day(RR1.26)
 Working >42hrs/wk(RR1.22)

11. Periodontal Care
 Risk of preterm birth is associated with severity of
periodontal disease
 Risk increases when periodontal disease progresses
in pregnancy
 Haematogenous transmission, or more likely, through
shared immunological response
 Randomized trials have not reported reduced rates of
preterm birth in women treated for periodontal
disease
 Effects of preconceptional periodontal care on
preterm birth not reported.

12.  Maternal Oral Therapy to Reduce Obstetric Risk Study were
published and showed that periodontal therapy did not reduce the
incidence of preterm delivery before 37, 35, or 32 weeks of
gestation, weight for gestational age, or neonatal morbidity.
 This is the largest randomized controlled trial of the effects of
maternal periodontal disease treatment on preterm birth rates; over
1800 pregnant women with periodontal disease were randomly
assigned to receive treatment before 24 weeks of gestation or
postpartum.
 Treatment consisted of up to four sessions of supra- and sub-
gingival scaling and root planing using hand and ultrasonic
instruments, full mouth tooth polishing, and oral hygiene instruction.
 Two subsequent large randomized trials of pregnant women with
periodontal disease had a similar design and also found that
treatment did not result in a significant improvement in any
pregnancy outcome.
 One of these, the Periodontal Infections and Prematurity Study
(PIPS), found that treatment might increase the risk of indicated
preterm birth; this requires further study

13. Asymptomatic Bacteruria
 Pregnant women with asymptomatic bacteriuria
should be treated with antibiotics to reduce the risk
of preterm birth.
 A meta-analysis of 14 randomized trials comparing
antibiotic treatment with placebo or no treatment in
pregnant women with asymptomatic bacteriuria
demonstrated that antibiotic treatment was effective
in:
(i) Clearing asymptomatic bacteriuria (OR 0.07, 95% CI
0.05-0.10),
(ii) reducing the incidence of pyelonephritis (OR 0.24,
95% CI 0.19-0.32), and
(iii) reducing preterm delivery and delivery of low-birth-
weight infants (OR 0.60, 95% CI 0.45-0.80)

14. Genital Tract Infections
 Chlamydia and gonorrhea — There is no
evidence that treatment of chlamydia or
gonorrhea prolongs gestation.
 The only controlled trial that evaluated the
effect of treatment of chlamydia on gestational
duration did not show a reduction in preterm
birth
 However, screening for and treatment of these
infections is recommended to prevent other
maternal and neonatal sequelae

15. Trichomanas
 The Vaginal Infections and Prematurity Study demonstrated that
pregnant women with Trichomonas vaginalis have a 30% higher risk
of having a preterm birth, a 2-fold risk of stillbirth or neonatal death,
and PPROM.
 Treatment of asymptomatic Trichomonas infection is not
recommended during pregnancy because it does not prevent, and
may even increase, the risk of preterm delivery

16. Bacterial Vaginosis
 Lactobacillus, which normally resides in the vaginal tract, is replaced
by Gardnerella vaginalis, Mobiluncus species, anaerobes, and
genital mycoplasmas
 Prevalence in pregnancy 10-20%; 50% asymptomatic
 Some randomized trials showed decrease in preterm labour up to
50%
(McGregor et al, Huth et al, Morales et.al)

17.  the largest trials studying treatment of asymptomatic BV during
pregnancy were done by McDonald et al [10] and Carey et al [11],
consisting of 879 women and 1953 women, respectively.
 They concluded that the treatment of asymptomatic bacterial
vaginosis in pregnant women does not reduce the rate of preterm
birth.
 A metaanalysis done by Leitich et al, involving 10 studies with
results for 3969 patients, showed that antibiotic treatment did not
decrease preterm birth in all patients combined (OR 0.83; 95% CI
0.57-1.21) or in high risk patients with previous preterm birth (OR
0.50; 95% CI 0.22-1.12).

18.  Klebanoff et. al –617 women with culture proven asymptomatic
infection at 16 to 23 weeks of gestation were randomly assigned to
receive either two doses of metronidazole (2 g) or placebo 48 hours
apart. All women were retreated with the same regimen at 24 to 29
weeks of gestation. Trichomonas resolved in 93 percent of
metronidazole treated women and 35 percent of the placebo group.
The rate of preterm birth was higher in treated than control women
(19 versus 11 percent, relative risk 1.8; 95% CI 1.2-2.7), primarily
related to an increased frequency of spontaneous preterm labor
(10.2 versus 3.5 percent, relative risk 3.0; 95% CI 1.5- 5.9).

19. UREAPLASMA UREALYTICUM
 Carey et al controlled for the presence of other organisms in 4934
women, and found there was no association between maternal
genital tract colonization with U. Urealyticum and low birthweight,
preterm birth or PPROM.
 In addition, a multicentre randomized trial of >900 patients with U.
Urealyticum (excluding those with C. trachomatis and GBS) found
there was no impact on adverse pregnancy outcomes when treated
with erythromycin vs placebo
Camille H. Raynes-Greenow et. al; Antibiotics for ureaplasma in the
vagina in pregnancy; Cochrane Systematic Review September 2004
– insufficient evidence

20. Malnutrition
1) Zinc
2) Polyunsaturated Fatty Acids (PUFA)

21. Benjamin W. Chaffee; Janet C. et.al; Effect of Zinc
Supplemntation on Pregnancy and infant outcome: Systemic
Review; Paediatric & Perinatal Epidemiology; Vol26, Issue
Supplemnt 51, P118-137 July 2012
 Zinc Supplementation is associated with a small, but
significant reduction in preterm birth (RR 0.86)
(5-50mg/day)
 Caulfield-82% of mothers have mild-moderate zinc deficiency
 Zinc is required for protein synthesis, cellular division and nuclic
acid metabolism
 Zinc Deficiency a/w fetal loss, congenital malformation, IUGR, low
BW, prolonged labour, preterm/post-term infants.
 Zinc supplementation a/w increase progesterone, better immune
function and better growth in child(though not in utero)

22.  Omega 3: Inhibits PgE2 & PgF2alpha
10x bluefish intake required (EPA:DHA
1:2.5); 1.6g/day to prolong pregnancy
4-6days.

23.  Women allocated to receive fish oil had a lower risk of
giving birth before 34 weeks of gestation (RR 0.69, 95%
CI 0.49-0.99; two trials, 860 women), but the proportion
delivering before 37 completed weeks was similar for
both groups. These results were largely due to one large
multicenter trial (Fish Oil Trials In Pregnancy [FOTIP])
 Supplementation with docosahexaenoic acid (n-3 long
chain polyunsaturated fatty acid) increased gestation by
a mean of six days in women who received it in fortified
eggs from 24 to 28 weeks of gestation until parturition
(133 mg in fortified eggs versus 33 mg in unfortified
eggs)

24. • Role of first trimester urine culture on all
pregnant women?
• Regular antenatal screening for women at
high-risk of asymptomatic bacteriuria eg,
women with sickle cell trait, recurrent
urinary tract infections, diabetes mellitus,
underlying renal disease

25. “MYTHS”
 Enhanced Prenatal Care (March of Dimes
Trial) and Social Support do no seem to
have an effect on preterm labour.
 Bed Rest, Hydration, hospitalization
 Measurement of uterine activity
 Abstinence
 Prophylactic antibiotics

26. Secondary Prevention
Risk Factors
 Fetal Anomalies
 History of prior preterm labour
 Mutiple gestation
 Polyhydramnios
 Intrauterine fetal demise
 Cervical Insufficiency
 Uterine Anomalies
 Placenta Previa/Abruptio Placenta
 Serious Maternal Disease
 Prior Cervical/Uterine manipulation
 Idiopathic

27. Diagnostic Tools
 Fetal Fibronectin Assay
 Assessment of Cervical Length

28. Fetal Fibronectin
 Extremely high negative predictive value.
 >99% of symptomatic patients with a negative
fFN overall will remain pregnant for at least 2
weeks
 Poor Positive Predictive value ~21% deliver
before 35wks
 Positive predictive value of ~35% if history of
preterm birth

29. Fetal Fibronectin
 In a secondary analysis of prospectively
collected data, quantitative fFN screening was
performed at 24 weeks' gestation,
(1) 0; (2)1 to 49; (3) 50 to 199; (4)200 ng/mL or
more.
 As the fFN concentration increased, rates of
recurrent PTB progressively rose
 Notably, 50% of asymptomatic patients with
high fFN levels (≥200 ng/mL) delivered prior to
34 weeks.

30. Cervical Length
 Normal cervical length – singleton vs multiple
gestation
 During TVS, if contractions present, observe
~3mins and take shortest cervical length
 Cervical length at 23wks is at or less than
25mm in 16% of the population

31. Correlation of cervical length at 22-24wks with
preterm delivery (before 33wks)
Cervical %Preterm Sensitivity Negative
Length PV
36-48mm 8
26-35mm 11 67
16-25mm 33 50 95.8%
<15mm 67 33 94.8%
Cerclage/progesterone/steroids not necessary if cervical length at or >15mm

32. Risks factors for short cervical
length in singleton pregnancies:
 Afro-Caribbean descent
 Teenagers
 Low ponderal index
 Hx of previous miscarriage
 Hx preterm delivery
 Drug abusers

33.  No established ideal time interval.
 Cervical length relatively stable over the 1st 2
trimesters
 Studies show that cervical length decreases at a
rate of 0.5mm/wk to 8mm/wk.
 Taking an average of 5mm/wk, 1wk is probably
too short a period – likely inter-observer error.
 Depending on cervical length at TVS and the
respective center’s threshold for intervention, an
appropriate time interval can be determined

34. Low risk pregnancies
 Positive predictive value only 4.5%
 No need for unnecessary
intervention/tocolytics/steroids.
High Risk Pregnancies: (Cervical length 2.5-3cm
<24wks)
 Sensitivity 60-80%
 Positive Predictive Value 55-70%
 Negative predictive value 89-94%
 No studies on effect of cervical length >24wks

35.  Cerclage
 Effective in High risk pregnancies (3 or
more preterm labours – refer to RCOG
May ’11 guideline
 History indicated, Ultrasound indicated
 Rescue cerclage

36. MANAGEMENT
 Progesterone
 Cervical Cerclage

37. Progesterone
 Steroid Hormone – 1934 isolated from
corpus luteum
 Natural or Synthetic formulations
 Oral, IM, Vaginal administrations
 Preterm birth rate:
25-31% versus 33-47% in controls

38. Progesterone - MOA
1) TH2 shift (less cell-mediated immune
response)
2) Progesterone induced blocking factor –
decreases decidual NK cell activity
3) Increases asymmetrical antibodies –
Masks fetal antigens

39. Progesterone - MOA
 Cervix
- Decreases cervical stromal degradation
- Barrier to ascending infection
- Inhibits cervical ripening
- Improves cervical length in short cervix
 Myometrium
- Decreases myometrial oxytocin receptors
- Decreases contraction frequency
 Decidua
- Attenuates response to haemorrhage and inflammation
 Fetal membranes + Placenta
- Suppress PG synthesis, decreases apoptosis

40. Progesterone Routes – Meis et. al
 Oral: Variable absorption and undergoes 1st pass
metabolism. Bioavailability uncertain and higher risk of
CNS sedation
 Vaginal: High endometrial concentration but difficult to
achieve constant blood levels
S/Es: 7.9% bloated, nausea, vaginal soreness
 Intramuscular: Slow-release; optimal blood levels.
S/Es: 19.1%; pain, injection site swelling, headache

41. (i)1 Previous Preterm Labour

42. Progesterone - Maternal-Fetal
Medicine Units Network trial
 Meis and coinvestigators randomly assigned 459 patients
with a documented history of spontaneous preterm
delivery to weekly intramuscular injections of 17-alpha-
hydroxyprogesterone caproate (250 mg) or placebo
 16 to 20 weeks of gestation and continuing until 36
weeks. Active prophylaxis significantly reduced the risk
of delivery:
- <37 weeks (36 versus 55 percent in the placebo group
[RR, 0.66; 95% CI, 0.54-0.81])
- <35 weeks (21 versus 31 percent [RR, 0.67; 95% CI,
0.48-0.93])
- <32 weeks (11 versus 20 percent [RR, 0.58; 95% CI,
0.37-0.91])

43. MFMU TRIAL (Cont)
Progesterone exposed infants had less perinatal
morbidity:
- significantly reduced rates of NEC
- IVH and
- need for supplemental oxygen.
* There was no evidence of virilization of female
offspring, which was a theoretic concern of this
therapy.

44. Progesterone:MFMU
Conclusion
 Singletons with prior Spontaneous Preterm Birth
can consider having IM 250mg 17P
administered weekly, from 16-20wks til 36wks.
 Singletons without prior SPTB but with incidental
findings of short cervix (CL<20mm) at 24wks –
Progesterone gel/suppository until 36/52
 No evidence of benefit in preventing preterm
labour in multiple gestations

45. Progesterone: Da Fonseca Trial
NEJM 2007; 357;462-9
 Randomly assigned 142 women at high-risk for preterm
delivery (based on at least one previous spontaneous
preterm birth, prophylactic cervical cerclage, or uterine
malformation) to daily supplementation with
progesterone vaginal suppositories (100 mg) or placebo
from 24 through 34 weeks of gestation.
 Active prophylaxis significantly reduced the risk of
delivery:
- <37 weeks (14 versus 29 percent in the placebo group)
- <34 weeks (3 versus 19 percent in the placebo group)
- (RR 0.54; NNT 1:7)

46. (ii) Incidental findings of Short
Cervix; No Hx of PTB

47.  If incidental findings of cervical length <25mm
20-24wks, for Vaginal suppository 200mg or gel
90mg daily til 36/52
 RR 0.50-0.60; NNT 1:14
- Romero et al;American Jouranl obstet Gynaec
2012; 206:124-144
- Hassan et al; U/S obstet Gynaecol 2011; 38:18
- SMFM clinical guidance may 2012

48.  Even if all eligible women received progesterone
prophylaxis, it would only reduce the overall
preterm birth rate in the United States by
approximately 2 percent (from 12.1 to 11.8
percent)
 22.5 percent of preterm births in 2002 were
recurrent and prophylaxis only reduces the
incidence of recurrent preterm birth by 33
percent.

49. Progesterone – No Benefit
 The most recent and largest Randomized
Trial did not find any benefit in preventing
recurent preterm birth
 659 women randomized to vaginal prog
gel 90mg nightly or placebo

50. (iii) Multiple Gestations
 Randomized trial 661 healthy women with twin
gestations compared outcomes of weekly intramuscular
injections of 250 mg of 17-alpha-hydroxyprogesterone
caproate or matching placebo, starting at 16 to 20 weeks
of gestation and ending at 35 weeks
 Delivery or fetal death before 35 weeks occurred in 41.5
percent of pregnancies in the progesterone group and
37.3 percent of those in the placebo group (RR 1.1; 95%
CI 0.9 to 1.3)
* STOPPIT Trial of 500 twin gestations – similar findings

51. (iv) PPROM
 No evidence to suggest any benefit
(V) Women with cerclage – no documented
benefit
(vi) Positive FFN – No Information

52. Follow-Up
4 year followup of 278 children exposed to
proluton antenatally:
 No difference in physical function, health
status, psychosocial performance

53. Price (USD)
Formulation/dose Retail Price Price per Total Cost
Dose (21wks)
Endometrin $157 for 21 $7.48 $1099.55
(100mg vaginal insert)
Prometrium $69 for 30 $2.30 $339.10
capsules
(100mg vaginal insert)
Crinone $170 per 10 $17.00 $2499
cubes
(90mg vaginal gel)
Prochieve $221 per $12.28 $1805.15
18cues
(90mg vaginal gel)
Makena $690 per $690 $14490
injection
(IM 250mg weekly)
Proluton $136 per 10 $13.60 $285.60
(IM 250mg compounded 17- injections
alpha-OH-progesterone caproate)

54. Tertiary Prevention
 Tocolytics
- Beta-2 Agonists
- Oxytocin Agonist
- Cox-2 Inhibitor
- Calcium Channel Blockers
- Nitric Oxide Donor
- Magnesium Sulphate

55. Tocolysis
The goals of treatment of PTL are:
 For Glucocorticoids to achieve optimum effect
 In-Utero Transfer
 Prolong pregnancy when there are underlying, self-
limited conditions
A systematic review noted that approximately 30 percent
of PTL cases spontaneously resolved. In subsequent
studies, 50 percent of patients hospitalized for PTL
deliver at term.

56. Contraindications
 Intrauterine fetal demise
 Lethal fetal anomaly
 Nonreassuring fetal status
 Severe fetal growth restriction
 Severe preeclampsia or eclampsia
 Maternal haemorrhage with nemodynamic
instability
 Chorioamnionitis

57. Efficacy of Tocolytics
 A meta-analysis of 58 randomized trials of tocolytic therapy of PTL
concluded all of the commonly used tocolytic agents were more
effective than placebo/no therapy for delaying delivery for 48 hours
or seven days (75-93% versus 53%)
 However, this prolongation of pregnancy was not associated with a
statistically significant reduction in overall rates of respiratory
distress syndrome or neonatal death.

58. Comparative efficacy
 Ritodrine and atosiban are licensed in the
UK for the treatment of threatened preterm
labour. Although the
 use of nifedipine for preterm labour is an
unlicensed indication it has the
advantages of oral administration and a
low purchase price.

59. Issues
 Beta-agonists have a high frequency of adverse effects.
 Nifedipine, atosiban and the COX inhibitors have fewer
types of adverse effects, and they occur less frequently
than for beta-agonists but how they compare with each
other is unclear.
 Using multiple tocolytic drugs appears to be associated
with a higher risk of adverse effects and so should be
avoided
 US: Indomethacin + MgSo4, if <32wks
(Issue: Indomethacin can cause earlier closure of ductus
arteriosus)
 Nifedipine +MgSo4 use – higher risk of chest pain and
ECG changes suggestive of myocardial ischaemia.

60. Antenatal Corticosteroids
 A single course of prenatal corticosteroids compared with placebo
has not been shown to be effective in babies who are born more
than seven days after treatment
 The Prenatal Repeat Corticosteroid International IPD Study Group:
assessing the effects using the best level of Evidence (PRECISE)
Group will conduct an IPD meta-analysis.
 The PRECISE International Collaborative Group was formed in
2010 and data collection commenced in 2011.
 Eleven trials with up to 5,000 women and 6,000 infants are eligible
for the PRECISE IPD meta-analysis.

61. The primary study outcomes for the infants will be:
 serious neonatal outcome (death, severe respiratory disease; severe
intraventricular haemorrhage (grade 3 and 4); chronic lung disease;
necrotising enterocolitis; serious retinopathy of prematurity; and cystic
periventricular leukomalacia);
 use of respiratory support (defined as mechanical ventilation or
continuous positive airways pressure or other respiratory support);
 and birth weight (Z-scores).

62.  For the children, the primary study outcomes will be
 death or
 any neurological disability (developmental delay or
intellectual impairment
 cerebral palsy
 blindness
 deafness
 For the women, the primary outcome will be
 maternal sepsis (defined as chorioamnionitis; pyrexia
after trial entry requiring the use of antibiotics; puerperal
sepsis; intrapartum fever requiring the use of antibiotics;
or postnatal pyrexia).

63. Choice of Agent
 Drug and dose — Two regimens of antenatal
glucocorticoid treatment have evolved and are
effective for accelerating fetal lung maturity:
 Betamethasone (two doses of 12 mg given
intramuscularly 24 hours apart)
 Dexamethasone (four doses of 6 mg given
intramuscularly 12 hours apart).
Higher or more frequent doses do NOT increase the
benefits of antenatal glucocorticoid therapy and
may increase the likelihood of adverse effects

64.  Reduction of IVH, NEC, NNM,
infection — (RR 0.4-0.6)
 Multiple Gestations: Blood levels of
bethametasone similar

65.  Several larger cohort and case control studie suggested
use of dexamethasone was neurotoxic and associated
with adverse neurologic outcomes compared to use
of betamethasone or no antenatal glucocorticoid
 Postnatal use of dexamethasone in premature infants
was associated with shorter stature, smaller head
circumference, poorer motor skills and coordination,
lower IQ scores, and an increased frequency of clinically
significant disabilities in survivors
 Sulfating agents in dexamethasone may be neurotoxic
 ?Insulin Resistance

66. Evidence from randomized trials
 Three large, multicenter randomized clinical
trials of single course versus multiple courses
of antenatal glucocorticoid therapy have been
reported:
1) the Maternal Fetal Medicine Units network
(MFMU) trial
2) Guinn et al multicenter trial
3) the Australasian Collaborative Trial of Repeat
doses of prenatal Steroids (ACTORDS)

67. Systemic Review
 Neonates exposed to repeat courses of glucocorticoids
had a reduction in RDS (RR 0.82, 95% CI 0.72-0.93) and
were less likely to have severe RDS (RR 0.60, 95% CI
0.48-0.75), particularly those infants delivered at the
earliest gestational ages (eg, less than 28 weeks of
gestation).
 Neonates exposed to repeat courses of glucocorticoids
were significantly less likely to have serious composite
morbidity (RR 0.79, 95% CI 0.67-0.93)
 No difference in maternal sepsis

68. MACS Trial
 This international multicenter placebo-controlled randomized
trial is the largest trial on this issue and included 1858
women between 25 to 32 weeks of gestation who remained
at risk for preterm birth 12 to 21 days after an initial course
of antenatal glucocorticoids.
 Repeat course of glucocorticoids or placebo every 14 days
to a maximum gestational age of 33 weeks.
 Repeated courses of glucocorticoids after the initial course
did not improve neonatal outcome, either composite or
individual parameters of morbidity, compared with placebo;
 Mortality was also similar for both groups. However,
neonates who received multiple courses of glucocorticoids
had significantly lower mean birthweight, length, and head
circumference than those in the placebo group.

69. ACTORDS
 In the ACTORDS trial, although multiple
steroid courses were associated with
decreased birth weight and head
circumference at birth, this was no longer
true at discharge, suggesting the potential
for catch up growth

70. Salvage (rescue) therapy
 Placebo-controlled randomized trial (Garite et al;
Obstetrix collaborative research network;imopact of
‘rescue course’ of antenatal corticosteroids; a multicenter
randomized placebo-controlled trial; Am J obstet
Gynecol 2009; 200;248.e1)
 a complete course of betamethasone (two 12 mg
injections) was offered to women <33 weeks of gestation
who were ≥14 days beyond a complete course of
antenatal glucocorticoids and at risk of delivery within the
next 7 days; women with PPROM were excluded
 (n = 437 pregnancies) showed a significant reduction in
the incidence of RDS (41.4 percent with betamethasone
versus 61.6 percent with placebo)

71. PPROM
 antenatal glucocorticoids for women with
preterm premature rupture of membranes
(Grade 1A ). We give them at 24 to 32 weeks of
gestation in the absence of any clinical signs of
chorioamnionitis.
• After 32wks, unless documented lung
prematurity, higher risk of choriomanionitis
negates the potential positive effects of repeated
steroids.
• (RCOG GTG recommends steroids til 34wks)

72. Preterm labor triage algorithm for high risk patients
Monica rincon, Leonardo Pereira; Ambulatory Mangement of Preterm Labor; Clinical Obstetrics and
Gynecology Volume 55 ; Sept 2012; Number 3;756-64
CL indicates cervical length by endocervical ultrasound; CX, cervix; CTXs, contractions; fFN, fetal
fibronectin; PG, progesterone; PPROM, preterm premature rupture of membrane; PTB, preterm birth;
PV, per vagina.

73. Recurrent preterm labor triage algorithm for patients who have
received antental corticosteroids.
(ACS indicates antenatal corticosteroids; CL, cervical length by
endocervical ultrasound; CX, cervix.)

74. Conclusions
1) Health policies are important (Europe)
2) Early Sex Education/Prenatal Counselling essential – Diet,
Prenatal periodontal care, instrumentation
3) No evidence for role of: bed rest, prophylactic antibiotics,
hydration, uterine activity monitors
4) Progesterone may beneficial in prolonging pregnancy, especially
in high risk groups, but data inconclusive
5) Role of cervical cerclage – history indicated or u/s indicated
6) Repeat course of antenal corticosteroids – exact dosage, timing
and long term effects debatable
7) PPROM – beyond 32wks?
8) Tocolytics – role of MgSo4 in neuroprotection <32wks?

75. References
1) Jay D Iams, Roberto Romero, Jennifer F Culhane et al; Lancet 2008;
371:164-175; Primary, Secondary and tertiary interventions to reduce
the morbidity and mortality of preterm birth.
2) ACOG Guidelines on antenal corticosteroid use 2012
3) Greentop guidelines
- Cervical Cerclage
- PPROM
- Tocolytics in preterm labour
4) Roberts, D, Dalziel, S. Antenatal corticosteroids for accelerating fetal lung maturation
for women at risk of preterm birth. Cochrane Database Syst Rev 2006;
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